@article{IBB_ID_54320, author={Caporale A, Monti A, Selis F, Sandomenico A, Tonon G, Ruvo M, Doti N}, title={A comparative analysis of catalytic activity and stability of microbial transglutaminase in controlled denaturing conditions}, date={2019 Aug 20}, journal={J Biotechnol (ISSN: 0168-1656linking)}, year={2019}, fullvolume={130}, volume={130}, pages={48--57}, url={}, abstract={Microbial transglutaminases (MTGs) catalyzes the formation of Gln-Lys isopeptide bonds and are widely used for the cross-linking of proteins and peptides in food and in biotechnological applications for bioconjugation reactions. In view of its practical utility, a comparative study of the catalytic activity and stability of the enzyme in a wide range of denaturing conditions has been performed through Circular Dichroism (CD), fluorescence and activity assays performed with model substrates. In agreement with previous results, we show that MTG has a significant structural and functional tolerance to pH changes, whereas the enzyme stability and activity decrease in presence of increasing amounts of denaturing agents, such as urea and guanidinium chloride (GdnHCl). Noteworthy, the activity of MTG in denaturing conditions differs markedly from that in pseudo-physiological settings, shifting unexpectedly toward higher substrate specificity. Also, the use of controlled amounts of denaturing agents (1.0-1.5M urea) largely improves yields and purity of the final products of 10-15% and 25-30%, respectively. These findings widen the range of applicability of the MTG-mediated biocatalysis for industrial and biotechnological purposes.}, keywords={Biocatalysis, Enzyme Stability, Protein Denaturation, Spectrometry, Fluorescence, Substrate Specificity, Transglutaminases, Chemistry, Metabolism, Bioconjugation, Chemical Denaturation, Circular Dichroism (cd), Fluorescence Spectroscopy, Microbial Transglutaminase (mtg), }, references={}, document_type={Journal Article, }, affiliation={IBB-CNR, Via Mezzocannone 16, 80134, Napoli, Italy., IBB-CNR, Via Mezzocannone 16, 80134, Napoli, Italy; Universita degli studi della Campania "Luigi Vanvitelli", Via Vivaldi n. 43 - 81100 Caserta, Caserta, Italy., BIOVIIIx, via Brin, 59, 80142, Napoli, Italy., IBB-CNR, Via Mezzocannone 16, 80134, Napoli, Italy. Electronic address: menotti.ruvo@unina.it., IBB-CNR, Via Mezzocannone 16, 80134, Napoli, Italy. Electronic address: nunzianna.doti@cnr.it., }, ibbaffiliation={1}, } @article{IBB_ID_10979, author={Sandomenico A, Severino V, Chambery A, Focà A, Focà G, Farina C, Ruvo M}, title={A Comparative Structural and Bioanalytical Study of IVIG Clinical Lots}, date={2013 Jul}, journal={Mol Biotechnol (ISSN: 1073-6085, 1559-0305electronic, 1073-6085linking)}, year={2013}, fullvolume={324}, volume={324}, pages={983--995}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882900813&partnerID=40&md5=8dd2160f2ef494b6d05f70b2d05f4233}, abstract={Intravenous immunoglobulin are important bio-therapeutics used in the replacement therapy for primary and secondary immunodeficiencies, chronic inflammatory disorders and several autoimmune haematologic disorders. Currently, a number of immunoglobulin intravenous (IVIG) products have been approved by the Food and Drug Administration (FDA) and are available commercially. It is known that small differences in the manufacturing processes as well as in the formulations may affect their clinical efficacy and tolerability. Therefore, given the complexity of the multi-step process required for the isolation of IVIG from human plasma, it is necessary to ensure a rigorous quality control of final products. We show here that a set of different bioanalytical techniques can be conveniently used to comparatively characterize, at a quantitative and qualitative level, different lots of IVIG preparations and to unveil randomly occurring impurities which can also affect the overall product stability. We have used circular dichroism, surface plasmon resonance and two-dimensional electrophoresis (2DE), and have demonstrated that this combination of bioanalytical approaches is very useful to improve the quality control of antibodies and to monitor the reliability of the IVIG manufacturing process.}, keywords={Biacore, Circular Dichroism, Ivig, Protein A, Thermal Denaturation, Electrophoresis, Industrial Engineering, Production Engineering, Quality Control, Surface Plasmon Resonance, Immunoglobulin, Analytical Research, Article, Qualitative Analysis, Quantitative Analysis, Two Dimensional Electrophoresis, Drug Contamination, Two-Dimensional, Humans, Immunoglobulin Fc Fragments, Intravenous, Protein Binding, Protein Stability, }, references={Kaveri, S.V., Maddur, M.S., Hegde, P., Lacroix-Desmazes, S., Bayry, Intravenous immunoglobulins in immunodeficiencies: More than mere replacement therapy (2011) Journal of Clinical and Experimental Immunology, 164 (SUPPL. 2), pp. 2-5. , 10.1111/j.1365-2249.2011.04387.x 1:CAS:528:DC%2BC3MXnvVehtLs%3 Navarro, R.P., Ballow, M., Fenrick, B., Pezalla, E.J., Considerations for the optimal use of immunoglobulin (2012) American Journal of Managed Care, 18 (SUPPL. 4), pp. 67-S78 Baerenwaldt, A., Biburger, M., Nimmerjahn, F., Mechanisms of action of intravenous immunoglobulins (2010) Expert Review of Clinical Immunology, 6 (3), pp. 425-434. , 10.1586/eci.10.9 1:CAS:528:DC%2BC3cXlsFOgsLk%3D Bayry, J., Fournier, E.M., Maddur, M.S., Vani, J., Wootla, B., Sibéril, S., Dimitrov, J.D., Kaveri, S.V., Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: A mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies (2011) Journal of Autoimmunity, 36 (1), pp. 9-15. , 10.1016/j.jaut.2010.09.006 1:CAS:528:DC%2BC3MXht1yls7Y%3D Radosevich, M., Burnouf, T., Intravenous immunoglobulin G: Trends in production methods, quality control and quality assurance (2010) Vox Sanguinis, 98 (1), pp. 12-28. , 10.1111/j.1423-0410.2009.01226.x 1:CAS:528:DC%2BC3cXhtFOktb8%3D Vermeer, A.W., Norde, W., The thermal stability of immunoglobulin: Unfolding and aggregation of a multi-domain protein (2000) Biophysical Journal, 78 (1), pp. 394-404. , 10.1016/S0006-3495(00)76602-1 1:CAS:528:DC%2BD3cXktFeqsQ%3D%3D Whitmore, L., Wallace, B.A., An online server for protein secondary structure analyses from circular dichroism spectroscopic data (2004) Nucleic Acids Research, 1 (WEB SERVER ISSUE 32), pp. 668-W673. , DICHROWEB 10.1093/nar/gkh371 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors (1991) Analytical Biochemistry, 198, pp. 268-277. , 10.1016/0003-2697(91)90424-R 1:CAS:528:DyaK3MXmslCrsb4%3D In accordance with EU pharmacopoeia: The values are stated in the leaflet accompanying the reference preparation (BRP - Batch 3). See also: British pharmacopoeia volume IV, appendix XIV Journal of Blood and Related Products Cohen, S., Sweeney, H.M., Modulation of Protein A Formation in Staphylococcus aureus by Genetic Determinants for Methicillin Resistance (1979) Journal of Bacteriology, 140 (3), pp. 1028-1035. , 1:CAS:528:DyaL3cXptVKrsg%3D%3D Velge-Roussel, F., Breton, P., Lescure, F., Guillon, X., Bout, D., Hoebeke, J., Analysis of human CD4-antibody interaction using the BIAcore system (1995) Journal of Immunological Methods, 183 (1), pp. 141-148. , 10.1016/0022-1759(95)00042-9 1:CAS:528:DyaK2MXmtVyku7g%3D Sandomenico, A., Monti, S.M., Marasco, D., Dathan, N., Palumbo, R., Saviano, M., Ruvo, M., IgE-binding properties and selectivity of peptide mimics of the FcvarepsilonRI binding site (2009) Molecular Immunology, 46 (16), pp. 3300-3390. , 10.1016/j.molimm.2009.07.025 1:CAS:528:DC%2BD1MXht1WhtLfI}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale Delle Ricerche, via Mezzocannone, 16, 80134 Naples, Italy CIRPeB, via Mezzocannone 16, 80134 Naples, Italy Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, via A. Vivaldi 43, 81100 Caserta, Italy Kedrion SpA, Loc. Ai Conti, 55051 Lucca Castelvecchio Pascoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53644, author={Russo R, Foca G, Rega C, Sandomenico A, Doti N, Mori F, Maddaluno M, Farina C, Ruvo M, Chambery A}, title={A multianalytical approach to investigate the effect of nanofiltration on plasma-derived factor IX clinical lots}, date={2017 Nov 20}, journal={Anal Biochem (ISSN: 0003-2697, 1096-0309electronic, 0003-2697linking)}, year={2017}, fullvolume={267}, volume={267}, pages={1--10}, url={}, abstract={Plasma-derived proteins are a subset of relevant biotherapeutics also known as "well-characterized biologicals". They are enriched from plasma through several steps of physical and biochemical methodologies, reaching the regulatory accepted standards of safety, levels of impurities, activity and lot-to-lot consistency. Final products accepted for commercialization are submitted to tight analytical, functional and safety controls by a number of different approaches that fulfill the requirements of sensitivity and reliability. We report here the use of a multianalytical approach for the comparative evaluation of different lots of Factor IX isolated from plasma preparations and submitted or not to a step of nanofiltration. The approach include, among the other, proteomic techniques based on both MALDI-TOF and LC-MS Orbitrap mass spectrometry, circular dichroism for structural characterization, chromatographic and electrophoretic techniques, ELISA and functional assays based on clotting activity and binding to known anticoagulants. Comparative data obtained on two sets of nanofiltered and non-nanofiltered lots with different final activity show that the products have substantially overlapping profiles in terms of activity, contaminants, structural properties and protein content, suggesting that the proposed multianalytical approach is robust enough to be used for the routine validation of clinical lots.}, keywords={Circular Dichroism, Fix, Mass Spectrometry, Proteomics, }, references={}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, DISTABIF, Universita della Campania Luigi Vanvitelli, Via Vivaldi, 43, 81100, Caserta, Italy., Istituto di Biostrutture e Bioimagini, CNR, IBB-CNR, Via Mezzocannone, 16, 80134, Napoli, Italy., Kedrion SpA, Via del Ciocco, 55051 Castelvecchio Pascoli Lucca, Italy., Istituto di Biostrutture e Bioimagini, CNR, IBB-CNR, Via Mezzocannone, 16, 80134, Napoli, Italy. Electronic address: menotti.ruvo@unina.it., Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, DISTABIF, Universita della Campania Luigi Vanvitelli, Via Vivaldi, 43, 81100, Caserta, Italy. Electronic address: angela.chambery@unicampania.it., }, ibbaffiliation={1}, } @article{IBB_ID_50853, author={Zaccaro L, Del Gatto A,  De Luca S, Ruvo M, Zannetti A, Del Vecchio S, Salvatore M, Pedone C, Saviano M}, title={A new and selective radiolabeled alpha(v)beta 3 peptide antagonist as tracer in tumor diagnosis}, date={2007}, journal={Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print)}, year={2007}, fullvolume={357}, volume={357}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_12755, author={De Luca S, Del Gatto A, Ruvo M, Panico M, Zannetti A, Del Vecchio S, Salvatore M, Pedone C, Saviano M, Zaccaro L}, title={A new and selective radiolabeled alpha(V)beta(3) peptide antagonist as tracer in tumor diagnosis}, date={2009}, journal={Adv Exp Med Biol (ISSN: 0065-2598, 0065-2598print)}, year={2009}, fullvolume={410}, volume={410}, pages={439--440}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-66349089137&partnerID=40&md5=12f11b77efa58322199373c9ed77e71b}, abstract={}, keywords={Vitronectin Receptor, Animal, Article, Drug Antagonism, High Performance Liquid Chromatography, Human, Mouse, Neoplasm, Positron Emission Tomography, Tumor Cell Line, High Pressure Liquid, Integrin Alphavbeta3, Positron-Emission Tomography, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Institute of Biostructures and Bioimaging, CNR, CIRPEB, Via Mezzocannone 16, 80134 Naples, Italy. }, ibbaffiliation={1}, } @article{IBB_ID_49164, author={Sandomenico A, Monti SM, Palumbo R, Ruvo M}, title={A New Fc Epsilon Ri Receptor-Mimetic Peptide (pepe) That Blocks Ige Binding To Its High Affinity Receptor And Prevents Mediator Release From Rbl 2h3 Cells}, date={2011 Sep}, journal={J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print)}, year={2011}, fullvolume={504}, volume={504}, pages={604--609}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79961167534&partnerID=40&md5=40819bd1b519b0d706180aaaa3caf0a7}, abstract={We have recently reported on a class of IgE-binding peptides designed based on the crystallographic structure of the high affinity Fc epsilon RI. Peptides contain receptor key residues located within the two distinct binding sites for IgE and selectively bind IgE with an affinity ranging between 6 and 60 mu M. We have here designed and characterized a new molecule containing the receptor loops C'-E and B-C and an optimized linker for joining them made of a Lys side chain and a beta-Ala. This new peptide shows an increased affinity (around 30 times) compared to the parent loop C'-E + B-C previously described, while retaining the same two-site mechanism of binding and the same selectivity. It also blocks the binding of IgE to the cell-anchored receptor and efficiently prevents histamine release from mast cells. These properties make the peptide a useful scaffold for the development of new anti-allergic drugs. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd}, keywords={Allergy, Fcεri, Histamine Release, Alanine, Fc Receptor, Fc Receptor Ii Epsilon, Immunoglobulin E, Lysine, Unclassified Drug, Animal Cell, Antigen Binding, Article, Controlled Study, Mast Cell, Mast Cell Degranulation, Molecular Mechanics, Nonhuman, Priority Journal, Receptor Binding, Amino Acid Sequence, Cell Line, Molecular Sequence Data, Peptides, }, references={Cookson, W., The alliance of genes and environment in asthma and allergy (1999) Nature, 402, pp. B5-B1 Meltzer, E.O., Grant, J.A., Impact of cetirizine on the burden of allergic rhinitis (1999) Ann. Allergy Asthma Immunol., 83, pp. 455-463 Kinet, J.P., The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology (1999) Annu. Rev. Immunol., 17, pp. 931-972 Kraft, S., Kinet, J.P., New developments in FcepsilonRI regulation, function and inhibition (2007) Nat. Rev. Immunol., 7, pp. 365-378 Garman, S.C., Kinet, J.P., Jardetzky, T.S., Crystal structure of the human high-affinity IgE receptor (1998) Cell, 95, pp. 951-961 Garman, S.C., Wurzburg, B.A., Tarchevskaya, S.S., Kinet, J.P., Jardetzky, T.S., Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha (2000) Nature, 406, pp. 259-266 Garman, S.C., Sechi, S., Kinet, J.P., Jardetzky, T.S., The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms (2001) J. Mol. Biol., 311, pp. 1049-1062 McDonnell, J.M., Calvert, R., Beavil, R.L., Beavil, A.J., Henry, A.J., Sutton, B.J., Gould, H.J., Cowburn, D., The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its high-affinity receptor FcepsilonRIalpha (2001) Nat. Struct. Biol., 8, pp. 437-441 Corren, J., Casale, T.B., Lanier, B., Buhl, R., Holgate, S., Jimenez, P., Safety and tolerability of omalizumab (2009) Clin. Exp. Allergy, 39, pp. 788-797 MacGlashan Jr, D., Therapeutic efficacy of omalizumab (2009) J. Allergy Clin. Immunol., 123, pp. 114-115 Buku, A., Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation (1999) Peptides, 20, pp. 415-420 Buku, A., Price, J.A., Mendlowitz, M., Masur, S., Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors and inhibits IgE binding (2001) Peptides, 22, pp. 1993-1998 Buku, A., Mendlowitz, M., Condie, B.A., Price, J.A., Histamine-releasing activity and binding to the FcepsilonRI alpha human mast cell receptor subunit of mast cell degranulating peptide analogues with alanine substitutions (2003) J. Med. Chem., 46, pp. 3008-3012 Buku, A., Condie, B.A., Price, J.A., Mezei, M., [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors (2005) J. Pept. Res., 66, pp. 132-137 Buku, A., Keselman, I., Lupyan, D., Mezei, M., Price, J.A., Effective mast cell degranulating peptide inhibitors of the IgE/Fc epsilonRI receptor interaction (2008) Chem. Biol. Drug Des., 72, pp. 133-139 Nakamura, G.R., Starovasnik, M.A., Reynolds, M.E., Lowman, H.B., A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor (2001) Biochemistry, 40, pp. 9828-9835 Nakamura, G.R., Reynolds, M.E., Chen, Y.M., Starovasnik, M.A., Lowman, H.B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc. Natl. Acad. Sci. U. S. A., 99, pp. 1303-1308 Rossi, M., Ruvo, M., Marasco, D., Colombo, M., Cassani, G., Verdoliva, A., Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide (2008) Mol. Immunol., 45, pp. 226-234 Stamos, J., Eigenbrot, C., Nakamura, G.R., Reynolds, M.E., Yin, J., Lowman, H.B., Fairbrother, W.J., Starovasnik, M.A., Convergent recognition of the IgE binding site on the high-affinity IgE receptor (2004) Structure, 12, pp. 1289-1301 Hamburger, R.N., Peptide inhibition of the Prausnitz-Küstner reaction (1975) Science, 189 (4200), pp. 389-390 Sandomenico, A., Monti, S.M., Marasco, D., Dathan, N., Palumbo, R., Saviano, M., Ruvo, M., IgE-binding properties and selectivity of peptide mimics of the FcvarepsilonRI binding site (2009) Mol. Immunol., 46, pp. 3300-3309 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors (1991) Anal. Biochem., 198, pp. 268-277 Cook, J.P., Henry, A.J., McDonnell, J.M., Owens, R.J., Sutton, B.J., Gould, H.J., Identification of contact residues in the IgE binding site of human FcepsilonRIalpha (1997) Biochemistry, 36, pp. 15579-15588 Henry, A.J., Cook, J.P., McDonnell, J.M., Mackay, G.A., Shi, J., Sutton, B.J., Gould, H.J., Participation of the N-terminal region of Cepsilon3 in the binding of human IgE to its high-affinity receptor FcepsilonRI (1997) Biochemistry, 36, pp. 15568-15578 Dearman, R.J., Skinner, R.A., Deakin, N., Shaw, D., Kimber, I., Evaluation of an in vitro method for the measurement of specific IgE antibody responses: the rat basophilic leukemia (RBL) cell assay (2005) Toxicology, 206, pp. 195-205 Meltzer, E. O., Grant, J. A., Impact of cetirizine on the burden of allergic rhinitis (1999) Ann. Allergy Asthma Immunol., 83, pp. 455-463 Kinet, J. P., The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology (1999) Annu. Rev. Immunol., 17, pp. 931-972 Garman, S. C., Kinet, J. P., Jardetzky, T. S., Crystal structure of the human high-affinity IgE receptor (1998) Cell, 95, pp. 951-961 Garman, S. C., Wurzburg, B. A., Tarchevskaya, S. S., Kinet, J. P., Jardetzky, T. S., Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha (2000) Nature, 406, pp. 259-266 Garman, S. C., Sechi, S., Kinet, J. P., Jardetzky, T. S., The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms (2001) J. Mol. Biol., 311, pp. 1049-1062 McDonnell, J. M., Calvert, R., Beavil, R. L., Beavil, A. J., Henry, A. J., Sutton, B. J., Gould, H. J., Cowburn, D., The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its high-affinity receptor FcepsilonRIalpha (2001) Nat. Struct. Biol., 8, pp. 437-441 Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E., Lowman, H. B., A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor (2001) Biochemistry, 40, pp. 9828-9835 Nakamura, G. R., Reynolds, M. E., Chen, Y. M., Starovasnik, M. A., Lowman, H. B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc. Natl. Acad. Sci. U. S. A., 99, pp. 1303-1308 Hamburger, R. N., Peptide inhibition of the Prausnitz-K stner reaction (1975) Science, 189 (4200), pp. 389-390 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Cook, J. P., Henry, A. J., McDonnell, J. M., Owens, R. J., Sutton, B. J., Gould, H. J., Identification of contact residues in the IgE binding site of human FcepsilonRIalpha (1997) Biochemistry, 36, pp. 15579-15588 Henry, A. J., Cook, J. P., McDonnell, J. M., Mackay, G. A., Shi, J., Sutton, B. J., Gould, H. J., Participation of the N-terminal region of Cepsilon3 in the binding of human IgE to its high-affinity receptor FcepsilonRI (1997) Biochemistry, 36, pp. 15568-15578 Dearman, R. J., Skinner, R. A., Deakin, N., Shaw, D., Kimber, I., Evaluation of an in vitro method for the measurement of specific IgE antibody responses: the rat basophilic leukemia (RBL) cell assay (2005) Toxicology, 206, pp. 195-205}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_50832, author={Verdoliva A, Marasco D, De Capua A, Saporito A, Bellofiore P, Manfredi V, Fattorusso R, Pedone C, Ruvo M}, title={A new ligand for immunoglobulin G subdomains by screening of a synthetic peptide library}, date={2005 Jul}, journal={Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-7633electronic)}, year={2005}, fullvolume={450}, volume={450}, pages={1242--1253}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-22144432202&partnerID=40&md5=db4053278754869bd8e60a7af6bc2992}, abstract={By screening a synthetic peptide library of general formula (NH2-Cys1-X2-X3-X4)(2)-Lys-G1y-OH, a disulfide-bridged cyclic peptide, where X2-X3-X4 is the tripeptide Phe-His-His, has been selected as a ligand for immunoglobulin G (IgG). The peptide, after a preliminary chromatographic characterization, has proved useful as a new affinity ligand for the purification of polyclonol as well as monoclonal antibodies from biological fluids, with recovery yields of up to 90% (90% purity). The ligand is able to bind antibody fragments containing both Fab and Fc from different antibody isotypes, a fact suggesting the presence of at least two different antibody-binding sites. While the recognition site on Fab is unknown, comparative binding studies with Fc, in association with the striking similarities of the peptide (named Fc-receptor mimetic, FcRM) with a region of the human FcyRIII receptor, strongly indicate that the peptide could recognize a short amino acid stretch of the lower hinge region, which has a key role in autoimmune disease triggering. The unique properties make the ligand attractive for both the purification of antibody fragments and as a lead for the generation of Fc-receptor antagonists.}, keywords={Affinity Purification, Antibodies, Immunoglobulins, Ligand Identification, Peptides, Fc Receptor, Immunoglobulin F(ab) Fragment, Immunoglobulin Fc Fragment, Monoclonal Antibody, Peptide Library, Polyclonal Antibody, Antibody Combining Site, Antigen Binding, Article, Comparative Study, Nuclear Magnetic Resonance, Priority Journal, Screening, Synthesis, Amino Acid Sequence, Animals, Biomimetic Materials, Blotting, Western, Chromatography, High Pressure Liquid, Enzyme-Linked Immunosorbent Assay, Humans, Models, Molecular, Molecular Sequence Data, Biomolecular, Cyclic, Rabbits, Sequence Alignment, Erratum, Immunoglobulin F (ab) Fragment, }, references={Padlan, E.A., (1994) Mol. Immunol., 31, pp. 169-21 Lories, R.J., Maertens, J.A., Ceuppens, J.L., Peetermans, W.E., (2000) Acta Clin. 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G., Santoro-Gazzano, H., Totpal, K., Wong, P. Y., Ultsch, M., Meng, Y. G., Mullkerrin, M. G., (2000) J. Immunol., 164, pp. 4178-4184 Delano, W. L., Ultsch, M. H., De Vos, A. M., Wells, J. A., (2000) Science, 287, pp. 1279-1283 Button, B. J., Beavil, R. L., Beavil, A., (2000) Br. Med. Bull., 56, pp. 1004-1018 Dijstelbloem, H. M., Van De Winkel, J. G. J., Kallenberg, C. G. M., (2001) Trends Immunol., 22, pp. 510-516 Martin, W. L., West, A. P., Gan Jr., L., Bjorkman, P. J., (2001) Mol. Cell, 7, pp. 867-877 Garman, S. C., Kinet, J. P., Jardetzky, T. S., (1998) Cell, 95, pp. 951-961 Garman, S. C., Wurzburg, B. A., Tarchevskaya, S. S., Kinet, J. P., Jardetzky, T. S., (2000) Nature, 406, pp. 259-266 Herr, A. B., Ballister, E. R., Bjorkman, P. J., (2003) Nature, 423, pp. 614-620 Rigby, L. J., Trist, H., Snider, J., Hulett, M. D., Hogarth, P. M., Epa, V. C., (2000) Allergy, 55, pp. 609-619 Nakamura, G. R., Reynolds, M. E., Chen, Y. M., Starovasnik, M. A., Lowman, H. B., (2002) Proc. Natl. Acad. Sci. USA, 99, pp. 1303-1308 Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E., Lowman, H. B., (2001) Biochemistry, 40, pp. 9828-9835 Lam, K. S., Salmon, S. E., Hersh, E. M., Hruby, V. J., Kazmierski, W. M., Knapp, R. J., (1991) Nature, 354, pp. 82-84 Rance, M., S rensen, O. W., Bodenhausen, G., Wagner, G., Ernst, R. R., W thrich, K., (1983) Biochem. Biophys. Res. Commun., 117, pp. 479-485 Bothener-By, A. A., Stephens, R. L., Lee, J., Warren, C. D., Jeanloz, R. W., (1984) J. Am. Chem. Soc., 106, pp. 811-813 G ntert, P., Braun, W., W thrich, K., (1991) J. Mol. Biol., 217, pp. 517-530}, document_type={Erratum, Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, Sezione Biostrutture, Via Mezzocannone 16, 80134, Napoli, Italy TECNOGEN S.C.p.A. Località la Fagianeria, 81015, Piana Di Monte Verna, Caserta, Italy Facoltà di Scienze Ambientali, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy TECNOGEN S. C. p. A. Localit la Fagianeria, 81015, Piana Di Monte Verna, Caserta, Italy Facolt di Scienze Ambientali, Seconda Universit di Napoli, Via Vivaldi 43, 81100 Caserta, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53569, author={Cimmino I, Lorenzo V, Fiory F, Doti N, Ricci S, Cabaro S, Liotti A, Vitagliano L, Longo M, Miele C, Formisano P, Beguinot F, Ruvo M, Oriente F}, title={A peptide antagonist of Prep1-p160 interaction improves ceramide-induced insulin resistance in skeletal muscle cells}, date={2017 Sep 22}, journal={Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking)}, year={2017}, fullvolume={254}, volume={254}, pages={71845--71858}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035096298&partnerID=40&md5=0d729b939d7cad7c5a8f7166678cd47d}, abstract={Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake. In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1.3- and 2.1-fold, respectively. The synthetic Prep1(54-72) peptide, mimicking the Prep1 region involved in the interaction with p160, reduces in vitro Prep1-p160 binding in a dose-dependent way (IC(50) = 0.20μM). In C2cer-treated L6 cells, 10μM Prep1(54-72) restores insulin signalling impaired by ceramide treatment. Prep1 overexpressing L6 cells display similar metabolic alterations observed in ceramide-treated L6 cells and the presence of Prep1(54-72) mitigates these events. All these findings suggest that disruption of the Prep1/p160 molecular interaction enhances insulin sensitivity impaired by ceramides in skeletal muscle cells and indicate this complex as an important target for type 2 diabetes.}, keywords={Prep1, Prep1(54-72) Peptide, Ceramide, Insulin Signalling, }, references={}, document_type={Journal Article, }, affiliation={Department of Translational Medicine, Federico II University of Naples and URT "Genomic of Diabetes" of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy., Institute of Biostructure and Bioimaging - National Research Council and Interuniversity Research Centre on Bioactive Peptides, Naples, Italy., Institute of Biostructure and Bioimaging, National Research Council and Interuniversity Research Centre on Bioactive Peptides, Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_9876, author={Pilla P, Sandomenico A, Malachovsk V, Borriello A, Giordano M, Cutolo A, Ruvo M, Cusano A}, title={A protein-based biointerfacing route toward label-free immunoassays with long period gratings in transition mode}, date={2012 Jan 15}, journal={Biosens Bioelectron (ISSN: 0956-5663, 1873-4235electronic, 0956-5663linking)}, year={2012}, fullvolume={373}, volume={373}, pages={486--491}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84455205468&partnerID=40&md5=56e0398e7269bc3f1d3c9865add5ae6e}, abstract={We present a fast and effective method for anchoring bioreceptors to optical waveguides exhibiting a poorly reactive polymer interface and that have to be minimally perturbed with respect to their design. The study originated from the need to biofunctionalize a fiber optic Long Period Grating (LPG) that is tuned in a highly sensitive working point, the so-called transition mode, through the deposition of a high refractive index overlay. In particular, a thin film of atactic polystyrene (PS) was dip-coated onto the LPG with a thickness suitable to optimize the LPG sensitivity to refractive index changes of the surrounding medium. Bovine serum albumin was selected as sacrificial layer for its well-known adhesion capabilities to PS surfaces, then glutaraldehyde was used to conjugate IgGs, serving as prototypical bioreceptor, on the device surface. The effectiveness of the immobilization method was assessed by studying the interaction between the immobilized IgG with a suitable anti-IgG. In a preliminary study performed by means of ELISA and surface plasmon resonance, optimal conditions for the biomolecular testing with the LPG were assessed. Four distinct interactions were thus monitored in real time following the shift of the LPG attenuation band. These experiments suggest a novel and interesting biofunctionalization approach of unreactive polymers with applications in immunosensing and basic life science research. (C) 2011 Elsevier BM. All rights reserved.}, keywords={Biomolecular Sensing, Immobilization Technique, Long Period Gratings, Modal Transition, Polymer Waveguides, Adhesion, Aldehydes, Body Fluids, Film Thickness, Optimization, Polystyrenes, Refractive Index, Surface Plasmon Resonance, Surface Testing, Transition Flow, Fiber Optic Sensors, Bovine Serum Albumin, Glutaraldehyde, Immunoglobulin G, Immunoglobulin G Antibody, Antigen Antibody Reaction, Article, Biological Activity, Chemical Labeling, Controlled Study, Enzyme Linked Immunosorbent Assay, Equipment Design, Immunoassay, Material Coating, Process Monitoring, Protein Assembly, Protein Immobilization, Reaction Optimization, Reaction Time, Refraction Index, Sensitivity Analysis, Surface Property, Transducer, Biosensing Techniques, Equipment Failure Analysis, Humans, Protein Array Analysis, Refractometry, Reproducibility Of Results, Sensitivity And Specificity, Staining And Labeling, }, references={Arnold, S., Khoshsima, M., Teraoka, I., Holler, S., Vollmer, F., (2003) Opt. Lett., 28, pp. 272-27 Chen, X., Zhang, L., Zhou, K., Davies, E., Sugden, K., Bennion, I., Hughes, M., (2007) Opt. Lett., 32, pp. 2541-2543 Corres, J.M., del Villar, I., Matias, I.R., Arregui, F.J., (2007) Opt. Lett., 32, pp. 29-31 Cusano, A., Iadicicco, A., Pilla, P., Contessa, L., Campopiano, S., Cutolo, A., Giordano, M., (2005) Opt. Lett., 30, pp. 2536-2538 DeLisa, M.P., Zhang, Z., Shiloach, M., Pilevar, S., Davis, C.C., Sirkis, J.S., Bentley, W.E., (2000) Anal. Chem., 72, pp. 2895-2900 Falciai, R., Mignani, A.G., Vannini, A., (2001) Sens. Actuators B, 74, pp. 74-77 Fan, X., White, I.M., Shopova, S.I., Zhu, H., Suter, J.D., Sun, Y., (2008) Anal. Chim. Acta, 620, pp. 8-26 Goddard, J.M., Hotchkiss, J.H., (2007) Prog. Polym. Sci., 32, pp. 698-725 Halldorsson, J., Arnfinnsdottir, N.B., Jonsdottir, A.B., Agnarsson, B., Leosson, K., (2010) Opt. Express, 18, pp. 16217-16226 He, Z., Tian, F., Zhu, Y., Lavlinskaia, N., Du, H., (2011), Biosens. Bioelectron, , in press, corrected proof. doi:10.1016/j.bios.2011.05.048Ichihashi, Y., Henzi, P., Bruendel, M., Mohr, J., Rabus, D.G., (2007) Opt. Lett., 32, pp. 379-381 James, S.W., Tatam, R.P., (2003) Meas. Sci. Technol., 14, pp. R49 Kawagoe, J.L., Niehaus, D.E., Wightman, R.M., (1991) Anal. Chem., 63, pp. 2961-2965 Kim, D.W., Zhang, Y., Cooper, K.L., Wang, A., (2006) Electron. Lett., 42, pp. 324-325 Kim, J.-W., Kim, K.-J., Yi, J.-A., Oh, M.-C., (2010) IEEE J. Sel. Top. Quant. Electron., 16, pp. 973-980 Landgraf, R., Kaiser, M.-K., Posseckardt, J., Adolphi, B., Fischer, W.-J., (2009) Procedia Chem., 1, pp. 1015-1018 Ma, H., Jen, A.K.-Y., Dalton, L.R., (2002) Adv. Mater., 14, pp. 1339-1365 Nguyen, A.-L., Luong, J.H.T., (1993) Biosens. Bioelectron., 8, pp. 421-431 Palmisano, F., Zambonin, P.G., Centonze, D., Quinto, M., (2002) Anal. Chem., 74, pp. 5913-5918 Pilla, P., Malachovská, V., Borriello, A., Buosciolo, A., Giordano, M., Ambrosio, L., Cutolo, A., (2011) Opt. Express, 19, pp. 512-526 Pilla, P., Manzillo, P.F., Giordano, M., Korwin-Pawlowski, M.L., Bock, W.J., Cusano, A., (2008) Opt. Express, 16, pp. 9765-9780 Rees, N.D., James, S.W., Tatam, R.P., Ashwell, G.J., (2002) Opt. Lett., 27, pp. 686-688 Rindorf, L., Jensen, J.B., Dufva, M., Pedersen, L.H., Höiby, P.E., Bang, O., (2006) Opt. Express, 14, pp. 8224-8231 Scriven, L.E., (1988) MRS Proc., 121, p. 717 Smietana, M., Bock, W.J., Mikulic, P., Ng, A., Chinnappan, R., Zourob, M., (2011) Opt. Express, 19, pp. 7971-7978 Spacková, B., Piliarik, M., Kvasnicka, P., Themistos, C., Rajarajan, M., Homola, J., (2009) Sens. Actuators B, 139, pp. 199-203 Wang, Z., Heflin, J.R., Stolen, R.H., Ramachandran, S., (2005) Appl. Phys. Lett., 86, p. 223104 Xin, Q., Wightman, R.M., (1997) Anal. Chim. Acta, 341, pp. 43-51}, document_type={Journal Article, }, affiliation={Optoelectronic Division, Engineering Department, University of Sannio, C.so Garibaldi 107, 82100 Benevento, Italy Institute of Biostructures and Bioimages, National Research Council, Via Mezzocannone 16, 80134 Napoli, Italy Institute of Composite and Biomedical Materials, National Research Council, P.le Tecchio 80, 80125 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54416, author={Doti N, Caporale A, Monti A, Sandomenico A, Selis F, Ruvo M}, title={A recent update on the use of microbial transglutaminase for the generation of biotherapeutics}, date={2020 Mar 14}, journal={World J Microbiol Biotechnol (ISSN: 0959-3993linking)}, year={2020}, fullvolume={64}, volume={64}, pages={53--53}, url={}, abstract={The recent scientific progresses on the use of enzyme-mediated reactions in organic, non-aqueous and aqueous media have significantly supported the growing demand of new biotechnological and/or pharmacological products. Today, a plethora of microbial enzymes, used as biocatalysts, are available. Among these, microbial transglutaminases (MTGs) are broadly used for their ability to catalyse the formation of an isopeptide bond between the γ-amide group of glutamines and the ε-amino group of lysine. Due to their promiscuity towards primary amine-containing substrates and the more stringent specificity for glutamine-containing peptide sequences, several combined approaches can be tailored for different settings, making MTGs very attractive catalysts for generating protein-protein and protein small molecule's conjugates. The present review offers a recent update on the modifications attainable by MTG-catalysed bioreactions as reported between 2014 and 2019. In particular, we present a detailed and comparative overview on the MTG-based methods for proteins and antibodies engineering, with a particular outlook on the synthesis of homogeneous antibody-drug conjugates.}, keywords={Bacteria Enzymology, Bacterial Proteins Metabolism, Biocatalysis, Biotechnology, Fungal Proteins Metabolism, Fungi Enzymology, Immunoconjugates Metabolism, Protein Engineering Methods, Substrate Specificity, Transglutaminases Metabolism, Antibody–drug Conjugate, Chemoenzymatic Reactions, Microbial Transglutaminase, Protein Bioconjugation, }, references={}, document_type={Journal Article, Review, }, affiliation={Institute of Biostructure and Bioimaging, CNR (IBB-CNR), Via Mezzocannone, 16, 80134, Naples, Italy. nunzianna.doti@cnr.it. Institute of Crystallography, CNR (IC-CNR), c/o Area Science Park s.s. 14 Km 163.5, Basovizza, 34149, Trieste, Italy. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABIF), University L. Vanvitelli, Via Vivaldi, 43, 80100, Caserta, Italy. BioVIIIx R&D, Via B. Brin, 59C, 80142, Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_48693, author={Lonardo E, Parish CL, Ponticelli S, Marasco D, Ribeiro D, Ruvo M, De Falco S, Arenas E, Minchiotti G}, title={A Small Synthetic Cripto Blocking Peptide Improves Neural Induction, Dopaminergic Differentiation, and Functional Integration of Mouse Embryonic Stem Cells in a Rat Model of Parkinson's Disease}, date={2010 Sep}, journal={Stem Cells (ISSN: 1066-5099)}, year={2010}, fullvolume={716}, volume={716}, pages={1326--1337}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77955786933&partnerID=40&md5=06fc54182f3d8174c573226542359b98}, abstract={Cripto is a glycosylphosphatidylinositol-anchored coreceptor that binds Nodal and the activin type I (ALK) -4 receptor, and is involved in cardiac differentiation of mouse embryonic stem cells (mESCs). Interestingly, genetic ablation of cripto results in increased neuralization and midbrain dopaminergic (DA) differentiation of mESCs, as well as improved DA cell replacement therapy (CRT) in a model of Parkinson's disease (PD). In this study, we developed a Cripto specific blocking tool that would mimic the deletion of cripto, but could be easily applied to embryonic stem cell (ESC) lines without the need of genetic manipulation. We thus screened a combinatorial peptide library and identified a tetrameric tripeptide, Cripto blocking peptide (BP), which prevents Cripto/ALK-4 receptor interaction and interferes with Cripto signaling. Cripto BP treatment favored neuroectoderm formation and promoted midbrain DA neuron differentiation of mESCs in vitro and in vivo. Remarkably, Cripto BP-treated ESCs, when transplanted into the striatum of PD rats, enhanced functional recovery and reduced tumor formation, mimicking the effect of genetic ablation of cripto. We therefore suggest that specific blockers such as Cripto BP may be used to improve the differentiation of ESC-derived DA neurons in vitro and their engraftment in vivo, bringing us closer towards an application of ESCs in CRT. 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K., Olale, F., Bennett, J. T., EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 (2003) Genes Dev, 17, pp. 31-36 Schier, A. F., Chemokine signaling: Rules of attraction (2003) Curr Biol, 13, pp. R192-R194 Gray, P. C., Harrison, C. A., Vale, W., Cripto forms a complex with activin and type II activin receptors and can block activin signaling (2003) Proceedings of the National Academy of Sciences of the United States of America, 100 (9), pp. 5193-5198. , DOI 10. 1073/pnas. 0531290100 Kelber, J. A., Shani, G., Booker, E. C., Vale, W. W., Gray, P. C., Cripto is a non-competitive activin antagonist that forms analogous signaling complexes with activin and nodal (2008) J Biol Chem, 283, pp. 4490-4500 Gray, P. C., Shani, G., Aung, K., Cripto binds transforming growth factor beta (TGF-beta) and inhibits TGF-beta signaling (2006) Mol Cell Biol, 26, pp. 9268-9278 Parish, C. L., Parisi, S., Persico, M. G., Cripto as a target for improving embryonic stem cell-based therapy in Parkinson's disease (2005) Stem Cells, 23, pp. 471-476 Sonntag, K. C., Simantov, R., Bjorklund, L., Context-dependent neuronal differentiation and germ layer induction of Smad4 (-/-) and Cripto (-/-) embryonic stem cells (2005) Mol Cell Neurosci, 28, pp. 417-429 Parish, C. L., Arenas, E., Stem-cell-based strategies for the treatment of parkinson's disease (2007) Neurodegenerative Diseases, 4 (4), pp. 339-347. , DOI 10. 1159/000101892 Li, J. Y., Christophersen, N. S., Hall, V., Critical issues of clinical human embryonic stem cell therapy for brain repair (2008) Trends Neurosci, 31, pp. 146-153. , Mar Jonsson, M. E., Ono, Y., Bjorklund, A., Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis (2009) Exp Neurol, 219, pp. 341-354 Villaescusa, J. C., Arenas, E., Transplantable midbrain dopamine neurons: A moving target (2010) Exp Neurol, 222, pp. 173-178 Sonntag, K. -C., Pruszak, J., Yoshizaki, T., Van Arensbergen, J., Sanchez-Pernaute, R., Isacson, O., Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin (2007) Stem Cells, 25 (2), pp. 411-418. , http: //stemcells. alphamedpress. org/cgi/reprint/25/2/411. pdf, DOI 10. 1634/stemcells. 2006-0380 Chiba, S., Lee, Y. M., Zhou, W., Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats (2008) Stem Cells, 26, pp. 2810-2820 Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling (2009) Nat Biotechnol, 27, pp. 275-280 Tam, J. P., Synthetic peptide vaccine design: Synthesis and properties of a high-density multiple antigenic peptide system (1988) Proc Natl Acad Sci USA, 85, pp. 5409-5413 Boheler, K. R., Crider, D. G., Tarasova, Y., Cardiomyocytes derived from embryonic stem cells (2005) Methods Mol Med, 108, pp. 417-435 Smidt, M. P., Smits, S. M., Burbach, J. P., Homeobox gene Pitx3 and its role in the development of dopamine neurons of the substantia nigra (2004) Cell Tissue Res, 318, pp. 35-43 Parish, C. L., Castelo-Branco, G., Rawal, N., Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice (2008) J Clin Invest, 118, pp. 149-160 Schein, J. C., Hunter, D. D., Roffler-Tarlov, S., Girk2 expression in the ventral midbrain, cerebellum, and olfactory bulb and its relationship to the murine mutation weaver (1998) Developmental Biology, 204 (2), pp. 432-450. , DOI 10. 1006/dbio. 1998. 9076 Adkins, H. B., Bianco, C., Schiffer, S. G., Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo (2003) J Clin Invest, 112, pp. 575-587 Chen, S., Do, J. T., Zhang, Q., Self-renewal of embryonic stem cells by a small molecule (2006) Proc Natl Acad Sci USA, 103, pp. 17266-17271 Inman, G. J., Nicolas, F. J., Callahan, J. F., SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7 (2002) Mol Pharmacol, 62, pp. 65-74 Kim, J. H., Auerbach, J. M., Rodriguez-Gomez, J. A., Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease (2002) Nature, 418, pp. 50-56}, document_type={Journal Article, }, affiliation={Stem Cell Fate Laboratory, Institute of Genetics and Biophysics, A. Buzzati-Traverso, CNR, Via Pietro Castellino 111, 80,131 Naples, Italy Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Florey Neuroscience Institutes, University of Melbourne, Parkville, VIC, Australia Centre for Neurosciences, University of Melbourne, Parkville, VIC, Australia Department of Biological Science, University of Naples, Napoli, Italy Institute of Biostructure and Bioimaging, CNR, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54582, author={Moreira M, Ruggiero A, Iaccarino E, Barra G, Sandomenico A, Ruvo M, Berisio R}, title={A structure-based approach for the development of a bicyclic peptide acting as a miniaturized anti-CD55 antibody}, date={2021 May 17}, journal={Int J Biol Macromol (ISSN: 0141-8130linking, 1879-0003electronic)}, year={2021}, fullvolume={6}, volume={6}, pages={1455--1462}, url={}, abstract={CD55 is a major regulator of the complement system, a complex network of proteins that cooperate to clear tissue and blood pathogens from the organism. Indeed, overexpression of CD55 is associated with many diseases and is connected to the resistance mechanisms exhibited by several cancers towards immunotherapy approaches. High level of CD55 expression on tumour cells renders it a good target for both imaging and immunotherapy. Indeed, a conceivable approach to tackle disease is to interfere with CD55-mediated complement regulation with the use of CD55-targeting antibodies. However, the large size and poor tissue penetration together with to the high costs of antibodies often limits their widespread therapeutic use. Here, we employed bioinformatic and chemical approaches to design and synthesize molecules of small dimensions able to mimic a CD55 blocking antibody. As a result, a bicyclic peptide, named as miniAB55, proved to bind CD55 with nanomolar affinity. This molecule represents an attracting chemical scaffold for CD55-directed diagnostic tools in diseases associated with CD55 overproduction. To further support the applicative potential of miniAB55, we prove that the miniAB55 binds CD55 on the same region involved in inactivation of the complement C3 and C5 convertases, thus opening promising scenarios for the development of complement-modulating tools.}, keywords={Biochemistry, Cancer, Immunity, Peptide, Protein Binding, Protein Structure, Amino Acid Sequence, Antibodies Pharmacology, Binding Sites, Antibody Immunology, Cd55 Antigens Chemistry Immunology, Cyclization, Humans, Kinetics, Miniaturization, Models, Molecular, Molecular Docking Simulation, Cyclic Chemistry}, references={}, document_type={Journal Article}, affiliation={Istituto di Biostrutture e Bioimmagini, C.N.R., Via Mezzocannone 16, I-80134 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53650, author={Leiria Campo V, Riul TB, Oliveira Bortot L, Martins-teixeira MB, Fiori Marchiori M, Iaccarino E, Ruvo M, Dias-baruffi M, Carvalho I}, title={A Synthetic MUC1 Glycopeptide Bearing betaGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells}, date={2017 Mar 16}, journal={Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-4227linking)}, year={2017}, fullvolume={1154}, volume={1154}, pages={527--538}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013130689&doi=10.1002%2fcbic.201600473&partnerID=40&md5=d1a3b158e2c674ae5968a9611a12c9ea}, abstract={This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing βGalNAc-SerOBn and βGalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr[αGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr[βGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing αGalNAc-Thr or βGalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with βGalNAc-glycopeptide 4-BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc-glycopeptide 3-BSA (1:40 000). Likewise, flow cytometry assays showed higher capacity of the obtained anti-glycopeptide 4-BSA antibodies to recognize MCF-7 tumor cells. Cross-recognition between immunopurified anti-βGalNAc antibodies and αGalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that βGalNAc-glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4-BSA, bearing βGalNAc-Thr as Tn antigen isomer. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords={Animals, Antibodies, Monoclonal, Metabolism, Antibody Formation, Drug Effects, Antigens, Tumor-Associated, Carbohydrate, Chemistry, Antineoplastic Agents, Chemical Synthesis, Pharmacology, Biological Assay, Standards, Carbohydrate Sequence, Humans, Isomerism, Mcf-7 Cells, Models, Molecular Dynamics Simulation, Mucin-1, Solid-Phase Synthesis Techniques, Surface Plasmon Resonance, Muc1-Mucins, Tn Antigen, Cancer Vaccines, Glycopeptides, Amino Acid Derivative, Antiserum, Freund Adjuvant, Monoclonal Antibody, Synthetic Peptide, Tumor Antigen, Antibody Production, Antibody Response, Article, Binding Affinity, Cancer Immunization, Controlled Study, Cross Reaction, Enzyme Linked Immunosorbent Assay, Glycosylation, Hydrogen Bond, Immunogenicity, Mcf-7 Cell Line, Priority Journal, Solid Phase Synthesis, Tandem Repeat, Tumor Cell, Bioassay, Biological Model, Carbohydrate Analysis, Mouse, }, references={Andrianifahanana, M., Moniaux, N., Batra, S.K., (2006) Biochim. 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Biol., 10, pp. 747-756 Coltart, D.M., Royyuru, A.K., Williams, L.J., Glunz, P.W., Sames, D., Kuduk, S.D., Schwarz, J.B., Live, D.H., (2002) J. Am. Chem. Soc., 124, pp. 9833-9844 Karsten, U., Serttas, N., Paulsen, H., Danielczyk, A., Goletz, S., (2004) Glycobiology, 14, pp. 681-692 Kinarsky, L., Suryanarayanan, G., Prakash, O., Paulsen, H., Clausen, H., Hanisch, F.G., Hollingsworth, M.A., Sherman, S., (2003) Glycobiology, 13, pp. 929-939 Schuman, J., Campbell, A.P., Koganty, R.R., Longenecker, B.M., (2003) J. Peptide Res., 61, pp. 91-108 Dziadek, S., Griesinger, C., Kunz, H., Reinscheid, U.M., (2006) Chem. Eur. J., 12, pp. 4981-4993 Matsushita, T., Ohyabu, N., Fujitani, N., Naruchi, K., Shimizu, H., Hinou, H., Nishimura, S.I., (2013) Biochemistry, 52, pp. 402-414}, document_type={Journal Article, }, affiliation={Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. Cafe S/N, CEP, 14040-903, Ribeirao Preto, Sao Paulo, Brazil., Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134, Napoli, Italy., Second University of Naples, via Vivaldi 43, 81100, Caserta, Italy., Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, Ribeirão Preto, São Paulo 14040-903, Brazil}, ibbaffiliation={1}, } @article{IBB_ID_53990, author={Scherino L, Giaquinto M, Micco A, Aliberti A, Bobeico E, La Ferrara V, Ruvo M, Ricciardi A, Cusano A}, title={A Time-Efficient Dip Coating Technique for the Deposition of Microgels onto the Optical Fiber Tip}, date={2018}, journal={Fibers}, year={2018}, fullvolume={208}, volume={208}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_50944, author={Giuffrida ML, Grasso G, Ruvo M, Pedone C, Saporito A, Marasco D, Pignataro B, Cascio C, Copani A, Rizzarelli E}, title={Abeta(25-35) And Its C- And/Or N-Blocked Derivatives: Copper Driven Structural Features And Neurotoxicity}, date={2007 Feb 15}, journal={Journal Of Neuroscience Research (ISSN: 0360-4012)}, year={2007}, fullvolume={577}, volume={577}, pages={623--633}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33847264869&partnerID=40&md5=347e83a5d413fa371eeae7868a1fe6c2}, abstract={The toxic properties of P-amyloid protein, A beta (1-42), the major component of senile plaques in Alzheimer's disease, depend on nucleation-dependent oligomerization and aggregation. In addition, A beta (1-42) toxicity is favored by the presence of trace metals, which affect the secondary structure of the peptide. A peptide comprising 11 residues within A beta (1-42) [A beta (25-35)] aggregates and retains the neurotoxic activity of A beta (1-42). We have used both A beta (25-35) and its C-amidated or N-acetylated/C-amidated derivatives to investigate the role of copper (II) in modulating the conformation and aggregation state as well as the neurotoxic properties of amyloid peptides. Electrospray ionization mass spectrometry (ESI-MS) and electron paramagnetic resonance (EPR) measurements were performed to verify the formation of copper (II) /A beta (25-35) complexes and to determine the coordination mode, respectively. A beta (2535) and its derivatives were analyzed by circular dichroism spectroscopy to assess their secondary structure, subjected to thioflavine-T (Th-T) binding assay to reveal beta-sheet structured aggregates formation, and imaged by scanning force microscopy. Toxicity was assessed on mature cultures of rat cortical neurons. We found that beta-sheet-structured species of A beta (25-35) were neurotoxic, whereas the random-coil-structured derivatives were devoid of effect. Interestingly, copper promoted the random-coiI/beta-sheet transition of A beta (25-35), with ensuing peptide toxicity, but it induced the toxicity of the N-acetylated/C-amidated derivative without affecting peptide folding. Moreover, copper did not influence either the folding or the activity of the C-amidated A beta (25-35), suggesting that blockade of the C-terminus of A beta peptides might be sufficient to prevent A beta toxicity. (c) 2006 Wiley-Liss, Inc}, keywords={β-Amyloid, Alzheimer, S Disease, Copper, Fibrils, Folding, Amyloid Beta Protein[25-35], Trace Metal, Amyloid Beta Protein (25 35), Amyloid Beta-Protein (25-35), Neurotoxin, Peptide Fragment, Unclassified Drug, Alzheimer Disease, Amino Terminal Sequence, Animal Cell, Article, Controlled Study, Electron Spin Resonance, Electrospray Mass Spectrometry, Neurotoxicity, Nonhuman, Oligomerization, Priority Journal, Protein Structure, Protein Synthesis, Scanning Force Microscopy, Animal Model, Atomic Force Microscopy, Brain Cortex, Chemistry, Circular Dichroism, Drug Effect, Nerve Cell, Pathology, Protein Conformation, Cerebral Cortex, Electron Spin Resonance Spectroscopy, Electrospray Ionization, Amyloid Beta Protein [25-35], }, references={Atwood, C.S., Moir, R.D., Huang, X., Scarpa, R.C., Bacarra, N.M., Hartshom, M.A., Tanzi, R.E., Bush, A.I., Drammatic aggregation of Alzheimer Abeta by Cu(II) is induced by condition representing physiological acidosis (1998) J Biol Chem, 273, pp. 12817-1282 Barrow, C.J., Yasuda, A., Kenny, P.T., Zagorski, M.G., Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. 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I., Drammatic aggregation of Alzheimer Abeta by Cu (II) is induced by condition representing physiological acidosis (1998) J Biol Chem, 273, pp. 12817-1282 Barrow, C. J., Yasuda, A., Kenny, P. T., Zagorski, M. G., Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra (1992) J Mol Biol, 225, pp. 1075-1093 Bondy, S. C., Guo-Ross, S. X., Truong, A. T., Promotion of transition metal-induced reactive oxygen species formation by beta-amyloid (1998) Brain Res, 799, pp. 91-96 Butterfield, D. A., Amyloid beta peptide (1-42) induced oxidative stress and neurotoxicity: Implication for neurodegeneration in Alzheimer's disease brain [review] (2002) Free Radic Res, 36, pp. 1307-1313 Cherny, R. A., Barnham, K. J., Bush, A. I., Cappai, R., Gautier Elisabeth, C. L., Masters, C. L., Carrington, D., Kok, G. B., PBT2, a novel MPAC for the treatment of Alzheimer's disease (2006) 10th International Conference on Alzheimer's Disease (ICAD), pp. P4-435 Curtain, C. C., Ali, F., Volitakis, I., Chemy, R. A., Norton, R. S., Beyreuther, K., Barrow, C. J., Barnham, K. J., Alzheimer's disease amyloid binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits (2001) J Biol Chem, 276, pp. 20466-20473 Deibel, M. A., Ehmann, W. D., Markesbery, W. R., Copper, iron and zinc imbalance in severely degenerated brain regions in Alzheimer's disease: Possible relation to oxidative stress (1996) J Neurol Sci, 143, pp. 137-142 Eckman, E. A., Reed, D. K., Eckman, C. B., Degradation of the Alzheimer's beta peptide by endothelin-converting enzyme (2001) J Biol Chem, 276, pp. 24540-24548 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amin acids (1990) Int J Pept Prot Res, 35, pp. 161-214 Garcia, V. J., Martinez, L., Brice o-Valero, J. M., Schilling, C. M., Dimensional metrology of nanometric spherical particles using AFM (1997) Probe Microsc, 1, p. 107 Joachim, C. L., Selkoe, D. J., The seminal role of -amyloid in the pathogenesis of Alzheimer disease (1992) Alzheimer Dis Assoc Disord, 6, pp. 7-34 Loo, D. T., Copani, A., Pike, C. J., Whittemore, E. R., Walencewicz, A. J., Cotman, C. W., Apoptosis is induced by -amyloid in cultured central nervous system neurons (1993) Proc Natl Acad Sci U S A, 90, pp. 7951-7955 Moir, R. D., Atwood, C. S., Romano, D. M., Laurans, M. H., Huang, X., Bush, A. I., Smith, J. D., Tanzi, R. E., Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations (1999) Biochemistry, 38, pp. 4595-4603 Moln r, Z. S., Kov cs, P., Laczk, I., So s, K., F l p, L., Penke, B., Lengyel, I., Enhanced G-protein activation by a mixture of A (25-35), A (1-40/42) and zinc (2004) J Neurochem, 89, pp. 1215-1223 Pike, C. J., Burdick, D., Walencewicz, A. J., Glabe, C. G., Cotman, C. W., Neurodegeneration induced by -amyloid peptides in vitro: The role of peptide assembly state (1993) J Neurosci, 13, pp. 1676-1687 Pike, C. J., Walencewicz-Wasserman, A. J., Kosmoski, J., Cribbs, D. H., Glabe, C. G., Cotman, C. W., Structure-activity analyses of beta-amyloid peptides: Contributions of the beta 25-35 region to aggregation and neurotoxicity (1995) J. Neurochem, 64, pp. 253-255 Rae, T. D., Schmidt, P. J., Pufhal, R. A., Culotta, V. C., O' Halloran, T. V., Undetectable intracellular free copper: The requirement of a copper chaperone for superoxide dismutase (1999) Science, 284, pp. 805-808 Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., Macgregor, L., Kiers, L., Masters, C. L., Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: A pilot phase 2 clinical trial (2003) Arch Neurol, 60, pp. 1685-1691 Saido, T. C., Yamao-Harigaya, W., Iwatsubo, T., Kawashima, S., Amino- and carboxyl-terminal heterogeneity of -amyloid peptides deposited in human brain (1996) Neurosci Lett, 215, pp. 173-176 Selkoe, D. J., Normal and abnormal biology of the -amyloid precursor protein (1994) Annu Rev Neurosci, 17, pp. 489-517 Selkoe, D. J., Translating cell biology into therapeutic advances in Alzheimer's disease [review] (1999) Nature, 399, pp. A23-A31 Simmons, M. A., Schneider, C. R., Amyloid -peptides act directly on single neurons (1993) Neurosci Lett, 150, pp. 133-136 Smith, D. P., Smith, D. G., Curtain, C. G., Boas, J., Pilbrow, J. R., Ciccotosto, G. D., Lau, T. L., Barnham, K. J., Copper-mediated amyloid- toxicity is associated with an intermolecular histidine bridge (2006) J Biol Chem, 281, pp. 15145-15154 Terzi, E., H lzemann, G., Seelig, J., Reversible random coil- -sheet transition of the -amyloid fragment (25-35) (1994) Biochemistry, 33, pp. 1345-1350 Valentine, J. S., Gralla, E. B., Delivering copper inside yeast and human cells (1997) Science, 278, pp. 817-818 Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M., Lomakin, A., Benedek, G. B., Teplow, D. B., Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates (1999) J Biol Chem, 274, pp. 25945-25952 White, A. R., Barnham, K. J., Bush, A. I., Metal homeostasis in Alzheimer's disease [review] (2006) Expert Rev Neurother, 6, pp. 711-722 Yankner, B. A., Duffy, L. K., Kirschner, D. A., Neurotrophic and neurotoxic effects of amyloid -protein: Reversal by tachykinin neuropeptides (1990) Science, 25, pp. 279-282 Zbilut, J. P., Colosimo, A., Conti, F., Colafranceschi, M., Manetti, C., Valerio, M., Webber Jr, C. L., Giuliani, A., Protein aggregation/folding: The role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and A (1-40) (2003) Biophys J, 85, pp. 3544-3557}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={PhD Program in Neurobiology, Faculty of Medicine, University of Catania, Catania, Italy I.B.B., CNR, Catania, Italy I.B.B., CNR, Napoli, Italy Department of Physical-Chemistry (F. Accascina), University of Palermo, Palermo, Italy Consorzio Catania Ricerche, Catania, Italy Department of Pharmaceutical Sciences, University of Catania, Catania, Italy Department of Chemical Sciences, University of Catania, Catania, Italy I. B. B., CNR, Catania, Italy I. B. B., CNR, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54451, author={Quassinti L, Gianfranceschi G, Cipiciani A, Caporale A, Ruvo M, Bramucci M}, title={AcGly-Phe-Asn(OH) and AcGly-Phe-Asn(NH(2)) tripeptides selectively affect the proliferation rate of MDA-MB 231 and HuDe cells}, date={2020 May}, journal={Mol Biol Rep (ISSN: 0301-4851linking)}, year={2020}, fullvolume={51}, volume={51}, pages={4009--4014}, url={}, abstract={There is increasing interest in the bioactivity of peptides carrying out antiproliferative, antihypertensive, antimicrobial, antioxidant, anticholesterolemic, opioid, and antidiabetic activities. The bioavailability of peptides depends on how readily they are digested by endopeptidases and their ability to pass through cell membranes, features that are determined by the peptide's chemical and physical structure. On the basis of structures present in peptides that have biological activity, particularly antiproliferative activity, the tripeptides AcGly-Phe-Asn(OH) and AcGly-Phe-Asn(NH(2)) have been designed and synthesized, then tested for their antiproliferative activity on human breast adenocarcinoma cells (MDA-MB 231) and human dermal fibroblasts (HuDe). The results show that the peptides significantly affect the proliferation of MDA-MB 231 and HuDe cells, with differentiated response between tumor and normal cells, and thus indicate that C-terminal amidation plays a role. Interestingly, the activity of both peptides in dermal fibroblasts follows the characteristic biphasic pattern of hormesis, a dose-response relationship.}, keywords={Antiproliferative Activity, Hormesis, N-Terminal Amidation, Tripeptide, }, references={}, document_type={Journal Article, }, affiliation={Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, via Gentile III da Varano, 1, Camerino, MC, 62032, Italy. Centro Studi "Giuseppe Gianfranceschi", Castelplanio, AN, 60031, Italy. Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, via Elce di Sotto, 8, Perugia, 06123, Italy. Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone, 16, Napoli, 80134, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_12385, author={Palmieri G, Bergamo P, Luini A, Ruvo M, Gogliettino M, Langella E, Saviano M, Hegde RN, Sandomenico A, Rossi M}, title={Acylpeptide hydrolase inhibition as targeted strategy to induce proteasomal down-regulation}, date={2011 Oct 10}, journal={Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking)}, year={2011}, fullvolume={399}, volume={399}, pages={e25888--e25888}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80053912078&partnerID=40&md5=0eb793207aa83ba1368c2b008d25af04}, abstract={Acylpeptide hydrolase (APEH), one of the four members of the prolyl oligopeptidase class, catalyses the removal of N-acylated amino acids from acetylated peptides and it has been postulated to play a key role in protein degradation machinery. Disruption of protein turnover has been established as an effective strategy to down-regulate the ubiquitin-proteasome system (UPS) and as a promising approach in anticancer therapy. Here, we illustrate a new pathway modulating UPS and proteasome activity through inhibition of APEH. To find novel molecules able to down-regulate APEH activity, we screened a set of synthetic peptides, reproducing the reactive-site loop of a known archaeal inhibitor of APEH (SsCEI), and the conjugated linoleic acid (CLA) isomers. A 12-mer SsCEI peptide and the trans10-cis12 isomer of CLA, were identified as specific APEH inhibitors and their effects on cell-based assays were paralleled by a dose-dependent reduction of proteasome activity and the activation of the pro-apoptotic caspase cascade. Moreover, cell treatment with the individual compounds increased the cytoplasm levels of several classic hallmarks of proteasome inhibition, such as NFkappaB, p21, and misfolded or polyubiquitinylated proteins, and additive effects were observed in cells exposed to a combination of both inhibitors without any cytotoxicity. Remarkably, transfection of human bronchial epithelial cells with APEH siRNA, promoted a marked accumulation of a mutant of the cystic fibrosis transmembrane conductance regulator (CFTR), herein used as a model of misfolded protein typically degraded by UPS. Finally, molecular modeling studies, to gain insights into the APEH inhibition by the trans10-cis12 CLA isomer, were performed. Our study supports a previously unrecognized role of APEH as a negative effector of proteasome activity by an unknown mechanism and opens new perspectives for the development of strategies aimed at modulation of cancer progression. © 2011 Palmieri et al.}, keywords={Acylamino Acid Releasing Enzyme, Caspase, Immunoglobulin Enhancer Binding Protein, Linoleic Acid, Proteasome, Protein P21, Small Interfering Rna, Transmembrane Conductance Regulator, Ubiquitin, Acylaminoacyl Peptidase, Acylaminoacyl-Peptidase, Archaeal Protein, Conjugated Linoleic Acid, Oligopeptide, Peptide Hydrolase, Proteinase Inhibitor, Article, Cancer Growth, Cell Assay, Concentration Response, Conjugation, Controlled Study, Cytoplasm, Down Regulation, Enzyme Activation, Enzyme Activity, Enzyme Inhibition, Epithelium Cell, Genetic Transfection, Isomer, Protein Degradation, Signal Transduction, Ubiquitination, Animal, Apoptosis, Binding Site, Cell Strain Caco 2, Chemical Structure, Chemistry, Drug Design, Drug Effect, Drug Interaction, Enzyme Specificity, Human, Isomerism, Metabolism, Mutation, Protein Conformation, Sulfolobus Solfataricus, Caco-2 Cells, Cystic Fibrosis Transmembrane Conductance Regulator, Down-Regulation, Models, Molecular, Protease Inhibitors, Proteasome Endopeptidase Complex, Proteolysis, Substrate Specificity, Time Factors, Pharmacology, Deficiency, }, references={Ciechanover, A., Proteolysis: from the lysosome to ubiquitin and the proteasome (2005) Nat Rev Mol Cell Biol, 6, pp. 79-8 Schwartz, A.L., Ciechanover, A., Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology (2009) Annu Rev Pharmacol Toxicol, 49, pp. 73-96 Shah, I.M., Di Napoli, M., The ubiquitin-proteasome system and proteasome inhibitors in central nervous system diseases (2007) Cardiovasc Hematol Disord Drug Targets, 7, pp. 250-273 Rajkumar, S.V., Richardson, P.G., Hideshima, T., Anderson, K.C., Proteasome inhibition as a novel therapeutic target in human cancer (2005) J Clin Oncol, 23, pp. 630-639 Naujokat, C., Sezer, O., Zinke, H., Leclere, A., Hauptmann, S., Proteasome inhibitors induced caspase-dependent apoptosis and accumulation of p21WAF1/Cip1 in human immature leukemic cells (2000) Eur J Haematol, 65, pp. 221-236 Drexler, H.C.A., Activation of the cell death program by inhibition of proteasome function (1997) Proc Natl Acad Sci USA, 94, pp. 855-860 Palombella, V.J., Rando, O.J., Goldberg, A.L., Maniatis, T., The ubiquitinproteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB (1994) Cell, 78, pp. 773-785 Nencioni, A., Grunebach, F., Patrone, F., Ballestrero, A., Brossart, P., Proteasome inhibitors: antitumor effects and beyond (2007) Leukemia, 21, pp. 30-36 Vlahakis, S.R., Badley, A.D., Influence of proteasome inhibitors on apoptosis (2006) Curr Opin Clin Nutr Metab Care, 9, pp. 42-47 Orlowski, R.Z., Kuhn, D.J., Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade (2008) Clin Cancer Res, 14, pp. 1649-1657 Landis-Piwowar, K.R., Milacic, V., Chen, D., Yang, H., Zhao, Y., The proteasome as a potential target for novel anticancer drugs and chemosensitizers (2006) Drug Resist Updat, 9, pp. 263-273 Serini, S., Piccioni, E., Merendino, N., Calviello, G., Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer (2009) Apoptosis, 14, pp. 135-152 Park, Y., Conjugated linoleic acid (CLA): Good or bad trans fat? 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Louis M. Staudt and Michael Karin) Bloom, J., Amador, V., Bartolini, F., DeMartino, G., Pagano, M., Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation (2003) Cell, 115, pp. 71-82 Moore, H.E., Davenport, E.L., Smith, E.M., Muralikrishnan, S., Dunlop, A.S., Aminopeptidase inhibition as a targeted treatment strategy in myeloma (2009) Mol Cancer Ther, 8, pp. 762-770 Wahle, K.W.J., Heys, S.D., Rotondo, D., Conjugated linoleic acids: are they beneficial or detrimental to health? (2004) Progr Lipid Res, 43, pp. 553-587 Reynolds, C.M., Roche, H.M., Conjugated linoleic acid and inflammatory cell signalling (2010) Prostaglandins Leukot Essent Fatty Acids, 82, pp. 199-204 Bartlam, M., Wang, G., Yang, H., Gao, R., Zhao, X., Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1 (2004) Structure, 12, pp. 1481-1488 Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Automated docking using Lamarckian genetic algorithm and an empirical binding free energy function (1998) J Comput Chem, 19, pp. 1639-1662 Sacchinettini, J.C., Scapin, G., Gopaul, D., Gordon, J.I., Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate (1992) J Biol Chem, 267, pp. 23534-23545 Hamilton, J.A., Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us (2004) Progr Lipid Res, 43, pp. 177-199 Nencioni, A., Grünebach, F., Patrone, F., Ballestrero, A., Brossart, P., Proteasome inhibitors: antitumor effects and beyond (2007) Leukemia, 21, pp. 30-36 Saric, T., Graef, C.I., Goldberg, A.L., Pathway for degradation of peptides generated by proteasomes: a key role for thimet oligopeptidase and other metallopeptidases (2004) J Biol Chem, 279, pp. 46723-46732 Ichinose, Y., Genka, K., Koike, T., Kato, H., Watanabe, Y., Randomized double-blind placebo controlled trial of bestatin in patients with resected stage I squamous-cell carcinoma (2003) J Natl Cancer Inst, 95, pp. 605-610 Perrier, J., Durand, A., Giardina, T., Puigserver, A., Catabolism of intracellular N-terminal acetylated proteins: involvement of acylpeptide hydrolase and acylase (2005) Biochimie, 87, pp. 673-685 Arnesen, T., van Damme, P., Polevoda, B., Helsens, K., Evjenth, R., Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans (2009) Proc Natl Acad Sci U S A, 106, pp. 8157-8162 Goetze, S., Qeli, E., Mosimann, C., Staes, A., Gerrits, B., Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster (2009) PLoS Biol, 7, pp. e1000236 Boissel, J.P., Kasper, T.J., Bunn, H.F., Cotranslational amino-terminal processing of cytosolic proteins. Cell-free expression of site-directed mutants of human hemoglobin (1988) J Biol Chem, 263, pp. 8443-8449 Kouzarides, T., Acetylation: a regulatory modification to rival phosphorylation? (2000) EMBO J, 19, pp. 1176-1179 Shimizu, K., Fujino, T., Ando, K., Hayakawa, M., Yasuda, H., Overexpression of oxidized protein hydrolase protect COS-7 cells from oxidative stress-induced inhibition of cell growth and survival (2003) Biochem Biophys Res Commun, 304, pp. 766-771 Ben Saadon, R., Fajerman, I., Ziv, T., Hellman, U., Schwartz, A.L., The tumor suppressor protein p16(INK4a) and the human papillomavirus oncoprotein-58 E7 are naturally occurring lysine-less proteins that are degraded by the ubiquitin system. Direct evidence for ubiquitination at the N-terminal residue (2004) J Biol Chem, 279, pp. 41414-41421 Hwang, C.S., Shemorry, A., Varshavsky, A., N-terminal acetylation of cellular proteins creates specific degradation signals (2010) Science, 327, pp. 973-977 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Decker, T., Lohmann-Matthes, M.L., A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity (1988) J Immunol Methods, 115, pp. 61-69 Koradi, R., Billeter, M., Wüthrich, K., MOLMOL: a program for display and analysis of macromolecular structures (1996) J Mol Graph, 14, pp. 51-55+29-32 Schwartz, A. L., Ciechanover, A., Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology (2009) Annu Rev Pharmacol Toxicol, 49, pp. 73-96 Shah, I. M., Di Napoli, M., The ubiquitin-proteasome system and proteasome inhibitors in central nervous system diseases (2007) Cardiovasc Hematol Disord Drug Targets, 7, pp. 250-273 Rajkumar, S. V., Richardson, P. G., Hideshima, T., Anderson, K. C., Proteasome inhibition as a novel therapeutic target in human cancer (2005) J Clin Oncol, 23, pp. 630-639 Drexler, H. C. A., Activation of the cell death program by inhibition of proteasome function (1997) Proc Natl Acad Sci USA, 94, pp. 855-860 Palombella, V. J., Rando, O. J., Goldberg, A. L., Maniatis, T., The ubiquitinproteasome pathway is required for processing the NF- B1 precursor protein and the activation of NF- B (1994) Cell, 78, pp. 773-785 Vlahakis, S. R., Badley, A. D., Influence of proteasome inhibitors on apoptosis (2006) Curr Opin Clin Nutr Metab Care, 9, pp. 42-47 Orlowski, R. Z., Kuhn, D. J., Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade (2008) Clin Cancer Res, 14, pp. 1649-1657 Landis-Piwowar, K. R., Milacic, V., Chen, D., Yang, H., Zhao, Y., The proteasome as a potential target for novel anticancer drugs and chemosensitizers (2006) Drug Resist Updat, 9, pp. 263-273 Hamel, F. G., Preliminary report: inhibition of cellular proteasome activity by free fatty acids (2009) Metabolism, 58, pp. 1047-1049 Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis (1990) Cell, 63, pp. 827-834 Ward, C. L., Omura, S., Kopito, R. R., Degradation of CFTR by the ubiquitin-proteasome pathway (1995) Cell, 83, pp. 121-127 Jensen, T. J., Loo, M. A., Pind, S., Williams, D. B., Goldberg, A. L., Multiple proteolytic systems, including the proteasome, contribute to CFTR processing (1995) Cell, 83, pp. 129-135 Chou, T. C., Talalay, P., Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors (1984) Adv Enzyme Regul, 22, pp. 27-55 Wertz, I. E., Dixit, V. M., Signaling to NF-kappaB: regulation by ubiquitination (2010) Cold Spring Harb Perspect Biol 2010 Mar, 2 (3), pp. a003350. , (Ed. Louis M. Staudt and Michael Karin) Moore, H. E., Davenport, E. L., Smith, E. M., Muralikrishnan, S., Dunlop, A. S., Aminopeptidase inhibition as a targeted treatment strategy in myeloma (2009) Mol Cancer Ther, 8, pp. 762-770 Wahle, K. W. J., Heys, S. D., Rotondo, D., Conjugated linoleic acids: are they beneficial or detrimental to health? (2004) Progr Lipid Res, 43, pp. 553-587 Reynolds, C. M., Roche, H. M., Conjugated linoleic acid and inflammatory cell signalling (2010) Prostaglandins Leukot Essent Fatty Acids, 82, pp. 199-204 Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Automated docking using Lamarckian genetic algorithm and an empirical binding free energy function (1998) J Comput Chem, 19, pp. 1639-1662 Sacchinettini, J. C., Scapin, G., Gopaul, D., Gordon, J. I., Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1. 75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate (1992) J Biol Chem, 267, pp. 23534-23545 Hamilton, J. A., Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us (2004) Progr Lipid Res, 43, pp. 177-199 Nencioni, A., Gr nebach, F., Patrone, F., Ballestrero, A., Brossart, P., Proteasome inhibitors: antitumor effects and beyond (2007) Leukemia, 21, pp. 30-36 Boissel, J. P., Kasper, T. J., Bunn, H. F., Cotranslational amino-terminal processing of cytosolic proteins. Cell-free expression of site-directed mutants of human hemoglobin (1988) J Biol Chem, 263, pp. 8443-8449 Hwang, C. S., Shemorry, A., Varshavsky, A., N-terminal acetylation of cellular proteins creates specific degradation signals (2010) Science, 327, pp. 973-977 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214}, document_type={Journal Article, }, affiliation={Institute of Protein Biochemistry, National Research Council (CNR-IBP), Napoli, Italy Institute of Food Sciences, National Research Council (CNR-ISA), Avellino, Italy Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli, Italy Institute of Crystallography, National Council of Research of Italy (CNR-IC), Bari, Italy Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54622, author={Monti A, Bruckmann C, Blasi F, Ruvo M, Vitagliano L, Doti N}, title={Amyloid-like Prep1 peptides exhibit reversible blue-green-red fluorescence in vitro and in living cells}, date={2021 Apr 18}, journal={Chem Commun (ISSN: 1359-7345linking, 1364-548xelectronic)}, year={2021}, fullvolume={15}, volume={15}, pages={3720--3723}, url={}, abstract={PREP1-based peptides form amyloid-like aggregates endowed with an intrinsic blue-green-red fluorescence with an unusual sharp maximum at 520 nm upon excitation with visible light under physiological conditions. The peptide PREP1[117-132], whose sequence does not contain aromatic residues, presents a pH-dependent and reversible fluorescence, in line with its structural transition from β-sheet rich aggregates to α-helix structures. These findings further demonstrate that the non-canonical fluorescence exhibited by amyloids is an articulated phenomenon.}, keywords={A549 Cells, Fluorescence, Homeodomain Proteins Chemistry, Humans, Hydrogen-Ion Concentration, Optical Imaging, Protein Aggregates, Protein Conformation}, references={}, document_type={Journal Article}, affiliation={Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone 16, Naples 80134, Italy. luigi.vitagliano@cnr.it nunzianna.doti@cnr.it.}, ibbaffiliation={1}, } @article{IBB_ID_12380, author={Doti N, Marasco D, Sabatella M, Monti SM, Dathan N, Viparelli F, Cassese A, Miele C, Pedone C, Ruvo M}, title={An analysis of deletion mutants of the PLD1 D4 domain defines short regions within the PLD1 interacting with PED/PEA15: implications for the development of peptides-specific antagonist}, date={2008 Sep}, journal={J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print)}, year={2008}, fullvolume={387}, volume={387}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_12403, author={Zhou JS, Sandomenico A, Burton O, Oettgen HC, Ruvo M}, title={An IgE receptor mimetic peptide (PepE) protects mice from IgE mediated anaphylaxis}, date={2013 Nov}, journal={Molecular Biosystems (ISSN: 1742-206x)}, year={2013}, fullvolume={406}, volume={406}, pages={2853--2859}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84885168763&partnerID=40&md5=2e0b01eae4f473d06f408c187fde5a2f}, abstract={Crosslinking of receptor-bound Immunoglobulin E (IgE) triggers immediate hypersensitivity reactions including anaphylaxis. Blocking the interaction of IgE with its high-affinity receptor, FceRI, on mast cells and basophils is an attractive strategy for the treatment of allergies. This approach has seen clinical success using the anti-IgE monoclonal antibody, omalizumab. We recently designed and characterized a novel FceRI-mimetic peptide (PepE) which contains the two key FceRI alpha-chain receptor loops known to interact with the e-heavy chain of IgE, C'-E and B-C, with an optimized linker for joining them. PepE has high specificity and affinity for IgE, blocks IgE binding to FceRI and prevents IgE-induced mediator release from RBL2H3 cells. We have now investigated the biological effects of this peptide in vivo using a line of mice (BALB/c Il4raF709) very sensitive to IgE-mediated systemic anaphylaxis. IgE-deficient (IgE(-/-)) Il4raF709 mice were passively sensitized with the anti-DNP IgE monoclonal antibody (SPE-7) and subsequently challenged i. v. with DNP-BSA. Mice receiving a single dose of PepE prior to sensitization with SPE-7 IgE were fully protected from anaphylaxis while vehicle control-treated mice displayed strong reactions with significant core body temperature drops and elevated levels of mouse mast cell protease-1 (mMCP-1) in the serum. However, PepE had no effect on IgE-mediated anaphylaxis if given after IgE administration in IgE(-/-) mice, suggesting that PepE can block binding of free IgE to FceRI but cannot compete with the receptor for already bound IgE in vivo. A single dose of PepE treatment did not protect IgE sufficient mice from IgE mediated anaphylaxis. However, a 3 week long course of PepE treatment protected IgE sufficient Il4raF709 mice from body temperature drops and elevation of serum mMCP-1. Our findings establish the potential of this type of structure for blocking IgE binding to mast cells in vivo and suggest that related peptides might have the potential to attenuate clinical allergic reactions.}, keywords={Immunoglobulin E, Immunoglobulin E Receptor, Peptide, Protein Binding, Amino Acid Sequence, Anaphylaxis, Animal, Chemistry, Disease Model, Female, Genetics, Immunology, Knockout Mouse, Metabolism, Molecular Mimicry, Article, Time Factors, Anaphylaxis Genetics Immunology Prevention, Control, Immunoglobulin E Genetics Immunology Metabolism, Peptides Administration, Dosage Chemistry Pharmacology, Protein Binding Immunology, Ige Chemistry, }, references={Burton, O.T., Oettgen, H.C., (2011) Immunol. Rev., 242, pp. 128-14 Galli, S.J.T., Tsai, M., (2012) Nat. Med., 18, pp. 693-704 Kraft, S., Kinet, J.P., (2007) Nat. Rev. Immunol., 7, pp. 365-378 Lieberman, J.A., Chehade, M., (2013) Curr. Allergy Asthma Rep., 13, pp. 78-84 Fried, A.J., Oettgen, H.C., (2010) Curr. Opin. Pediatr., 22, pp. 758-764 Wastling, J.M., Scudamore, C.L., Thornton, E.M., Newlands, G.F., Miller, H.R., (1997) Immunology, 90, pp. 308-313 Helm, B., Kebo, D., Vercelli, D., Glovsky, M.M., Gould, H., Ishizaka, K., Geha, R., Ishizaka, T., (1989) Proc. Natl. Acad. Sci. U. S. A., 86, pp. 9465-9469 Rigby, L.J., Trist, H., Snider, J., Hulett, M.D., Hogarth, P.M., Epa, V.C., (2000) Allergy, 55, pp. 609-619 Stamos, J., Eigenbrot, C., Nakamura, G.R., Reynolds, M.E., Yin, J., Lowman, H.B., Fairbrother, W.J., Starovasnik, M.A., (2004) Structure, 12, pp. 1289-1301 Buku, A., Keselman, I., Lupyan, D., Mezei, M., Price, J.A., (2008) Chem. Biol. Drug Des., 72, pp. 133-139 Buku, A., Price, J.A., Mendlowitz, M., Masur, S., (2001) Peptides, 22, pp. 1993-1998 Nakamura, G.R., Starovasnik, M.A., Reynolds, M.E., Lowman, H.B., (2001) Biochemistry, 40, pp. 9828-9835 Sandomenico, A., Monti, S.M., Marasco, D., Dathan, N., Palumbo, R., Saviano, M., Ruvo, M., (2009) Mol. Immunol., 46, pp. 3300-3309 Mathias, C.B., Hobson, S.A., Garcia-Lloret, M., Lawson, G., Poddighe, D., Freyschmidt, E.J., Xing, W., Oettgen, H.C., (2011) J. Allergy Clin. Immunol., 127, pp. 795-805. , e791-e796 Fields, G.B., Noble, R.L., (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Oettgen, H.C., Martin, T.R., Wynshaw-Boris, A., Deng, C., Drazen, J.M., Leder, P., (1994) Nature, 370, pp. 367-370 Hayashi, N., Tsukamoto, Y., Sallas, W.M., Lowe, P.J., (2007) Br. J. Clin. Pharmacol., 63, pp. 548-561 Bedoret, D., Singh, A.K., Shaw, V., Hoyte, E.G., Hamilton, R., Dekruyff, R.H., Schneider, L.C., Umetsu, D.T., (2012) Mucosal Immunol., 5, pp. 267-276}, document_type={Journal Article, Research Support, N. I. H. , Extramural, Non-U. S. Gov'T, }, affiliation={Boston Children's Hospital, Boston MA 02115, United States Boston Medical Center, Boston University School of Medicine, Boston MA 02118, United States Istituto di Biostrutture e Bioimmagini, CNR, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, I-80134 Naples, Italy Seconda Università di Napoli, via Vivaldi 43, Caserta Napoli, Italy Seconda Universit di Napoli, via Vivaldi 43, Caserta Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_12420, author={Ponticelli S, Takeda A, Mitola S, Stassen J, Presta M, Ambati J, Ruvo M, De Falco S, Marasco D}, title={Angiogenesis modulation: identification of tetrameric tripeptide as inhibitor of VEGFR-1 by the screening of peptide combinatiorial libraries}, date={2008 Sep}, journal={J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print)}, year={2008}, fullvolume={311}, volume={311}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_9127, author={Rossi M, Ruvo M, Marasco D, Colombo M, Cassani G, Verdoliva A}, title={Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide}, date={2008 Jan}, journal={Mol Immunol (ISSN: 0161-5890)}, year={2008}, fullvolume={415}, volume={415}, pages={226--234}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34548305099&partnerID=40&md5=bbbcbbec674f0b3d7ccd524ecba53032}, abstract={Using a combinatorial chemistry approach, we identified a tetrameric tripeptide, denoted Protein A Mimetic (PAM) or TG19318, able to bind to immunoglobulins of different classes and species. The inverso variant, with the tripeptide in the all-D configuration (D-PAM or TG19320) is described as retaining binding properties to Ig. This peptide has now been assayed as a binder for E class immunoglobulins, in linear and competitive ELISA experiments. dot-blot and surface plasmon resonance (SPR) analyses. We show that D-PAM binds IgE with high specificity and selectivity. the interaction being sufficient to inhibit anaphylactic release of beta-hexosaminidase from RBL 2H3 cells, with an IC50 value of 10 mu g/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 mu g/kg dose of peptide, while its intraperitoneal injection inhibits mouse PCA with an IC50 of about 7 mg/kg and an efficacy comparable to that of ketotifen. Similarly, D-PAM inhibits ACA in the mouse, with 50% suppression at 10 mg/kg. The results presented here show that the peptide is active on the studied models, with effective doses below toxicity level, hence the molecule is a promising candidate for development of a new class of anti-allergic drugs. (C) 2007 Elsevier Ltd. All rights reserved.}, keywords={Active Cutaneous Anaphylaxis, Allergic Disorders, Passive Cutaneous Anaphylaxis, Antiallergic Agent, Beta N Acetylhexosaminidase, Binding Protein, Immunoglobulin E, Ketotifen, Tg 19320, Tg19318, Unclassified Drug, Animal Cell, Animal Experiment, Animal Model, Article, Atopy, Controlled Study, Drug Dose Increase, Enzyme Linked Immunosorbent Assay, Female, Mast Cell Degranulation, Mouse, Nonhuman, Passive Skin Anaphylaxis, Priority Journal, Protein Analysis, Protein Binding, Protein Determination, Protein Variant, Surface Plasmon Resonance, 4-Dinitrophenol, Anti-Allergic Agents, Biotinylation, Peptides, Protein Conformation, Rattus, }, references={Adkinson, N.F., Eggleston, P.A., Eney, D., Goldstain, E.O., Schuberth, K.C., Bacon, J.R., Hamilton, R.G., Wheeler, B., A controlled trial of immunotherapy for asthma in allergic children (1997) N. Engl. J. 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B, 749, pp. 233-242 Verdoliva, A., Pannone, F., Rossi, M., Catello, S., Manfredi, V., Affinity purification of polyclonal antibodies using a new all-D synthetic peptide ligand: comparison with protein A and protein G (2002) J. Immunol. Methods, 271, pp. 77-88 Wiegand, T.W., Williams, P.B., Dreskin, S.C., Jouvin, M.H., Kinet, J.P., Tasset, D., High-affinity oligonucleotide ligands to human IgE Inhibit binding to Fcε Receptor I (1996) J. Immunol., 157, pp. 221-230 Yamanishi, R., Kondo, K., Tsuji, H., Ogawa, T., Micro-assay to Measure the allergenicity of Kunitz-type Soybean Trypsin Inhibitor toward Balb/c Mice by Using RBL-2H3 Cells (1995) Biosci. Biotech. Biochem., 59, pp. 1272-1275 Yan, H., Lamm, M.E., Björling, E., Huang, Y.T., Multiple functions of immunoglobulin A in mucosal defense against viruses: an in vitro measles virus model (2002) J. Virol., 76, pp. 10972-10979 Adkinson, N. F., Eggleston, P. A., Eney, D., Goldstain, E. O., Schuberth, K. C., Bacon, J. R., Hamilton, R. G., Wheeler, B., A controlled trial of immunotherapy for asthma in allergic children (1997) N. Engl. J. Med., 336, pp. 324-33 Alter, B. P., Gaston, T., Lipton, J. M., Lack of effect of corticosteroids in W/Wv and S1/S1d mice: these strains are not a model for steroid-responsive Diamond-Blackfan anemia (1993) Eur. J. Haematol., 50, pp. 275-278 Barnes, P. J., Pedersen, S., Busse, W. W., Efficacy and safety of inhaled corticosteroids: an update (1998) Am. J. Respir. Crit. Care Med., 157, pp. S1-S53 Barnes, P. J., Therapeutic strategies for allergic diseases (1999) Nature, 402 (SUPPL), pp. B31-B38 Baylink, D. J., Glucocorticoid-induced osteoporosis (1983) N. Engl. J. Med., 309, pp. 306-308 Kinet, J. P., Blank, U., Brini, A., Jouvin, M. H., Kuster, H., Mejan, O., Ra, C., The high-affinity receptor for immunoglobulin E: a target for therapy of allergic diseases (1991) Int. Arch. Allergy Appl. Immunol., 94, pp. 51-55 Lee, E., Choi, E. J., Cheong, H., Kim, Y. -R., Ryu, S. Y., Kim, K. -M., Anti-allergic actions of the leaves of Castanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation (1999) Arch. Pharm. Res., 22, pp. 320-323 Marshall, G. D., Therapeutic options in allergic disease: antihistamines as systemic antiallergic agents (2000) J. Allergy Clin. Immunol., 106, pp. 303-309 Meltzer, E. O., Grant, J. A., Impact of ceterizine on the burden of allergic rhinitis (1999) Ann. Allergy Asthma Immunol., 83, pp. 455-463 Michaelsen, T. E., Ihle, ., Beckstr m, K. J., Herstad, T. K., Kolberg, J., H iby, E. A., Aase, A., Construction and functional activities of chimeric mouse-human immunoglobulin G and immunoglobulin M antibodies against the Neisseria meningitidis PorA P1. 7 and P1. 16 epitopes (2003) Infect. Immun., 71, pp. 5714-5723 Nakamura, G. R., Starovasnik, A., Reynolds, M. E., Lowman, H. B., A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor (2001) Biochemistry, 40, pp. 9828-9835 Nakamura, G. R., Reynolds, M. E., Chen, Y. M., Starovasnik, M. A., Lowman, H. B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc. Natl. Acad. Sci. U. S. A., 99, pp. 1303-1308 Piper, J. M., Ray, W. A., Daugherty, J. R., Griffin, M. R., Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs (1991) Ann. Intern. Med., 114, pp. 735-740 Presta, L. G., Lahr, S. J., Shields, R. L., Porter, J. P., Gorman, C. M., Fendly, B. M., Jardieu, P. M., Humanization of an antibody direct against IgE (1993) J. Immunol., 151, pp. 2623-2632 Rigby, L. J., Trist, H., Snider, J., Hulett, M. D., Hogarth, P. M., Monoclonal antibodies and synthetic peptides define the active site of FcepsilonRI and a potential receptor antagonist (2000) Allergy, 55, pp. 609-619 Till, S. J., Francis, J. N., Nouri-Aria, K., Durham, S. R., Mechanisms of immunotherapy (2004) J. Allergy Clin. Immunol., 113, pp. 1025-1034 van der Kleij, H. P., Kraneveld, A., van Houwelingen, A. H., Kool, M., Weitemberg, A. C., Redegeld, F. A., Nijkamp, F. P., Murine model for non-IgE-mediated asthma (2004) Inflammation, 28, pp. 115-125 Wiegand, T. W., Williams, P. B., Dreskin, S. C., Jouvin, M. H., Kinet, J. P., Tasset, D., High-affinity oligonucleotide ligands to human IgE Inhibit binding to Fc Receptor I (1996) J. Immunol., 157, pp. 221-230 Yan, H., Lamm, M. E., Bj rling, E., Huang, Y. T., Multiple functions of immunoglobulin A in mucosal defense against viruses: an in vitro measles virus model (2002) J. Virol., 76, pp. 10972-10979}, document_type={Journal Article, }, affiliation={Tecnogen S.p.A., Localita La Fagianeria, 81015 Piana di Monte Verna, CE, Italy Tecnogen S. p. A., Localita La Fagianeria, 81015 Piana di Monte Verna, CE, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10973, author={Altieri F, Di Stadio CS, Severino V, Sandomenico A, Minopoli G, Miselli G, Di Maro A, Ruvo M, Chambery A, Quagliariello V, Masullo M, Rippa E, Arcari P}, title={Anti-amyloidogenic property of human gastrokine}, date={2014 Nov}, journal={Biochimie (ISSN: 0300-9084, 1638-6183, 0300-9084linking)}, year={2014}, fullvolume={480}, volume={480}, pages={91--100}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84908005465&partnerID=40&md5=8f0ecc092b7da77c3db3ba71919b5454}, abstract={Gastrokine 1 (GKN1) is a stomach-specific protein expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids also found in several unrelated proteins associated with major human diseases like BRI2, related to familial British and Danish dementia and surfactant protein C (SP-C), associated with respiratory distress syndrome. It was reported that recombinant BRICHOS domains from BRI2 and SP-C precursor (proSP-C) prevent fibrils formation of amyloid-beta peptide (A beta), that is the major component of extracellular amyloid deposits in Alzheimer's disease. Here we investigated on the interaction between human recombinant GKN1 (rGKN1) and A beta peptide (1-40) that derives from the partial hydrolysis of the amyloid precursor protein (APP). GKN1 prevented amyloid aggregation and fibrils formation by inhibiting A beta (1-40) polymerization, as evaluated by SDS-PAGE, thioflavin-T binding assay and gel filtration experiments. Mass spectrometry showed the formation of a prevailing 1: 1 complex between GKN1 and A beta (1-40). SPR analysis of GKN1/A beta interaction led to calculate a dissociation constant (K-D) of 34 mu M. Besides its interaction with A beta (1-40), GKN1 showed also to interact with APP as evaluated by confocal microscopy and Ni-NTA pull-down. Data strongly suggest that GKN1 has anti-amyloidogenic properties thus functioning as a chaperone directed against unfolded segments and with the ability to recognize amyloidogenic polypeptides and prevent their aggregation. (C) 2014 Elsevier B. V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved}, keywords={Amyloidogenesis, Aβ Peptide, Brichos Domain, Gastric Cancer, Gastrokine 1, Amyloid Beta Protein[1-40], Amyloid Precursor Protein, Chaperone, Cystatin, Nitrilotriacetate Nickel, Polypeptide, Recombinant Gastrokine 1, Recombinant Protein, Surfactant Protein C, Thioflavine, Unclassified Drug, Article, Binding Assay, Confocal Microscopy, Controlled Study, Drug Activity, Fiber, Human, Human Cell, Hydrolysis, Mass Spectrometry, Neuroblastoma Cell Line, Polyacrylamide Gel Electrophoresis, Polymerization, Protein Aggregation, Protein Binding, Protein Expression, Protein Protein Interaction, Protein Secondary Structure, Stomach Adenocarcinoma, Surface Plasmon Resonance, Z Peptide, Aß Peptide, A Peptide, Amyloid Beta Protein [1-40], Amino Acid Sequence , Amyloid Chemistry Metabolism , Amyloid Beta-Peptides Chemistry Metabolism , Amyloid Beta-Protein Precursor Metabolism , Tumor , Molecular Sequence Data , Peptide Fragments Chemistry Metabolism , Peptide Hormones Genetics Metabolism Pharmacology , Protein Aggregates Drug Effects , Recombinant Proteins Metabolism Pharmacology , Sequence Homology, Matrix-Assisted Laser Desorption-Ionization, }, references={Martin, T.E., Powell, C.T., Wang, Z., Bhattacharyya, S., Walsh-Reitz, M.M., Agarwal, K., Toback, F.G., A novel mitogenic protein that is highly expressed in cells of the gastric antrum mucosa (2003) Am. J. Physiol. Gastrointest. Liver Physiol., 285 (2), pp. 332-G34 Nardone, G., Rippa, E., Martin, G., Rocco, A., Siciliano, R.A., Fiengo, A., Cacace, G., Arcari, P., Gastrokine 1 expression in patients with and without Helicobacter pylori infection (2007) Dig. Liver Dis., 39 (2), pp. 122-129 Nardone, G., Martin, G., Rocco, A., Rippa, E., La Monica, G., Caruso, F., Arcari, P., Molecular expression of gastrokine 1 in normal mucosa and in Helicobacter pylori-related preneoplastic and neoplastic lesions (2008) Cancer Biol. Ther., 7 (12), pp. 1890-1895 Moss, S.F., Lee, J.W., Sabo, E., Rubin, A.K., Rommel, J., Westley, B.R., May, F.E., Resnick, M.B., Decreased expression of gastrokine 1 and the trefoil factor interacting protein TFIZ1/GKN2 in gastric cancer: Influence of tumor histology and relationship to prognosis (2008) Clin. 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Gov'T, }, affiliation={Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini 5Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of NaplesCaserta, Italy Institute of Biostructures and Bioimaging-IBB, CNRNaples, Italy IRCCS MultimedicaMilan, Italy Laboratory of Biotechnology, Department of Anesthesia, Surgical and Emergency Sciences, Second University of Naples, Via Costantinopoli 16Naples, Italy Department of Motor Sciences and Wellness, University of ParthenopeNaples, Italy CEINGE, Advanced Biotechnology Scarl, Via Gaetano Salvatore 486Naples, Italy IRCCS Multimedica, Milan, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53318, author={Palumbo R, Gogliettino M, Cocca E, Iannitti R, Sandomenico A, Ruvo M, Balestrieri M, Rossi M, Palmieri G}, title={APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome}, date={2016 Sep 23}, journal={Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking)}, year={2016}, fullvolume={320}, volume={320}, pages={N/D--N/D}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85016421215&doi=10.3390%2fijms17101614&partnerID=40&md5=2663773d29edf4d6992a4bbc3fab59b3}, abstract={The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH-proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-kappaB, p21(Waf1), and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies.}, keywords={Acylpeptide Hydrolase (apeh), Anti-Tumoral Target, Osteosarcoma Cell Lines, Peptide Inhibitor, Proteasome, }, references={}, document_type={Journal Article, }, affiliation={Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. rosanna.palumbo@cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marta.gogliettino@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. ennio.cocca@ibbr.cnr.it., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. robertaiannitti@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. annamaria.sandomenico@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. menotti.ruvo@unina.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marco.balestrieri@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. mose.rossi@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. gianna.palmieri@ibbr.cnr.it., }, ibbaffiliation={1}, } @article{IBB_ID_53861, author={Caporale A, Doti N, Monti A, Sandomenico A, Ruvo M}, title={Automatic procedures for the synthesis of difficult peptides using oxyma as activating reagent: A comparative study on the use of bases and on different deprotection and agitation conditions}, date={2018 Apr}, journal={Peptides (ISSN: 1873-5169electronic, 0196-9781linking)}, year={2018}, fullvolume={301}, volume={301}, pages={38--46}, url={}, abstract={Solid-Phase Peptide Synthesis (SPPS) is a rapid and efficient methodology for the chemical synthesis of peptides and small proteins. However, the assembly of peptide sequences classified as "difficult" poses severe synthetic problems in SPPS for the occurrence of extensive aggregation of growing peptide chains which often leads to synthesis failure. In this framework, we have investigated the impact of different synthetic procedures on the yield and final purity of three well-known "difficult peptides" prepared using oxyma as additive for the coupling steps. In particular, we have comparatively investigated the use of piperidine and morpholine/DBU as deprotection reagents, the addition of DIPEA, collidine and N-methylmorpholine as bases to the coupling reagent. Moreover, the effect of different agitation modalities during the acylation reactions has been investigated. Data obtained represent a step forward in optimizing strategies for the synthesis of "difficult peptides".}, keywords={Bases, Difficult Peptide Sequences, Oxyma, Solid Phase Peptide Synthesis (spps), }, references={}, document_type={Journal Article, }, affiliation={IBB-CNR, Via Mezzocannone 16, 80134 Napoli, Italy; CIRPeB, Via Mezzocannone 16, 80134 Napoli, Italy., IBB-CNR, Via Mezzocannone 16, 80134 Napoli, Italy; CIRPeB, Via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: nunzianna.doti@cnr.it., IBB-CNR, Via Mezzocannone 16, 80134 Napoli, Italy; DiSTABiF, Universita degli Studi della Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy., IBB-CNR, Via Mezzocannone 16, 80134 Napoli, Italy; CIRPeB, Via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: menotti.ruvo@unina.it., }, ibbaffiliation={1}, } @article{IBB_ID_53321, author={Alterio V, Cadoni R, Esposito D, Vullo D, Fiore AD, Monti SM, Caporale A, Ruvo M, Sechi M, Dumy P, Supuran CT, De Simone G, Winum JY}, title={Benzoxaborole as a new chemotype for carbonic anhydrase inhibition}, date={2016 Sep 29}, journal={Chem Commun (ISSN: 1359-7345, 1364-548x, 1364-548xelectronic)}, year={2016}, fullvolume={357}, volume={357}, pages={11983--11986}, url={http://pubs.rsc.org/en/content/articlelanding/2016/cc/c6cc06399c#!divRelatedContent}, abstract={In this paper we report the synthesis of a series of benzoxaborole derivatives, their inhibition properties against some carbonic anhydrases (CAs), recognized as important drug targets, and the characterization of the binding mode of these molecules to the CA active site. Our data provide the first experimental evidence that benzoxaboroles can be efficiently used as CA inhibitors.}, keywords={, }, references={V. Alterio, A. Di Fiore, K. D'Ambrosio, C. T. Supuran and G. De Simone, Chem. Rev. , 2012, 112 , McDonald, A. Oloumi, S. Chia, C. Ostlund, A. Ahmadi, A. Kyle, U. Auf dem Keller, S. Leung, D. Huntsman, B. Clarke, B. W. Sutherland, D. Waterhouse, M. Bally, C. Roskelley, C. M. Overall, A. Minchinton, F. Pacchiano, F. Carta, A. Scozzafava, N. Touisni, J. Y. Winum, C. T. Supuran and S. Dedhar, Cancer Res. , 2011, 71 , 3364. Scozzafava, J. L. Montero and C. T. Supuran, Biorg. Med. Chem. , 2009, 17 , 3649. Winum, R. A. Hall, F. A. Muhlschlegel, A. Scozzafava and C. T. Supuran, Bioorg. Med. Chem. Lett. , 2009, 19 , 2642. Wang, H. Li, J. Shi, J. Wang, Z. Liu, S. Chen, S. Hu and Y. Zhu, Biorg. Med. Chem. , 2016, 24 , 2576. Kauffman, Cancer Invest. , 2004, 22 , 304. Daniels, J. Labutti, I. Parsons, D. Nix, E. Baronas, F. Hsieh, L. S. Gan and G. Miwa, Drug metabolism and disposition: the biological fate of chemicals , 2005, 33 , 771. Plattner and S. Chanda, Environ. Mol. Mutagen. , 2013, 54 , 338. Snyder, J. 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Lebedev, N. S. Pannu, R. A. Steiner, R. A. Nicholls, M. D. Winn, F. Long and A. A. Vagin, Acta Crystallogr. D Biol. Crystallogr. , 2011, 67 , 355. Ballard, K. D. Cowtan, E. J. Dodson, P. Emsley, P. R. Evans, R. M. Keegan, E. B. Krissinel, A. G. Leslie, A. McCoy, S. J. McNicholas, G. N. Murshudov, N. S. Pannu, E. A. Potterton, H. R. Powell, R. J. Read, A. Vagin and K. S. Wilson, Acta Crystallogr. D Biol. Crystallogr. , 2011, 67 , 235. Jones and A. Liljas, Proteins , 1988, 4 , 274. Plattner, B. Nare, S. A. Wring, D. Chen, Y. Freund, E. G. Gaukel, M. D. Orr, J. B. Perales, M. Jenks, R. A. Noe, J. M. Sligar, Y. K. Zhang, C. J. Bacchi, N. Yarlett and R. Don, Future Med. Chem. , 2011, 3 , 1259. Wong, S. Farr-Jones, A. B. Shenvi and C. A. Kettner, Biochemistry , 1988, 27 , 7689. D. G. Hall and S. J. Benkovic, ACS Med. Chem. Lett. , 2012, 3 , 48. }, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimagini-CNR, Naples, Italy.  Institut des Biomolécules Max Mousseron (IBMM) UMR5247 CNRS, ENSCM, Université de Montpellier, Montpellier, France. Laboratorio di Chimica Bioinorganica, Polo Scientifico, Università degli Studi di Firenze, Sesto Fiorentino, Florence, Italy. Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Sassari, Italy. Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze, Sesto Fiorentino, Florence, Italy. }, ibbaffiliation={1}, } @article{IBB_ID_54031, author={Farina B, Sturlese M, Mascanzoni F, Caporale A, Monti A, Sorbo GD, Fattorusso R, Ruvo M, Doti N}, title={Binding mode of AIF(370–394) peptide to CypA: insights from NMR, label-free and molecular docking studies}, date={2018}, journal={Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking)}, year={2018}, fullvolume={691}, volume={691}, pages={2377--2393}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85051177492&doi=10.1042%2fBCJ20180177&partnerID=40&md5=b69faf0f0dd9df3f2ccbce71c5118f55}, abstract={The complex formation between the proteins apoptosis-inducing factor (AIF) and cyclophilin A (CypA) following oxidative stress in neuronal cells has been suggested as a main target for reverting ischemia-stroke damage. Recently, a peptide encompassing AIF residues 370–394 has been developed to target the AIF-binding site on CypA, to prevent the association between the two proteins and suppress glutamate-induced cell death in neuronal cells. Using a combined approach based on NMR spectroscopy, synthesis and in vitro testing of all Ala-scan mutants of the peptide and molecular docking/molecular dynamics, we have generated a detailed model of the AIF (370–394)/CypA complex. The model suggests us that the central region of the peptide spanning residues V374–K384 mostly interacts with the protein and that for efficient complex inhibition and preservation of CypA activity, it is bent around amino acids F46–G75 of the protein. The model is consistent with experimental data also from previous works and supports the concept that the peptide does not interfere with other CypA activities unrelated to AIF activation; therefore, it may serve as an ideal template for generating future non-peptidic antagonists. © 2018 The Author(s).}, keywords={Alanine, Amino Acid, Apoptosis Inducing Factor, Cyclophilin A, Amino Terminal Sequence, Article, Carboxy Terminal Sequence, Cell Death, Circular Dichroism, Molecular Docking, Molecular Dynamics, Molecular Model, Mutagenesis, Nuclear Magnetic Resonance Spectroscopy, Nuclear Overhauser Effect, Peptide Synthesis, Preservation, Priority Journal, Protein Binding, Protein Conformation, Protein Protein Interaction, }, references={Sevrioukova, I.F., Apoptosis-inducing factor: Structure, function, and redox regulation (2011) Antioxid. 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Marzolo 5, Padova, 35131, Italy Advanced Accelerator Applications (AAA), Via Vivaldi, 43, Caserta, 81100, Italy Istituto di Biochimica delle Proteine (IBP)-CNR, Via Pietro Castellino, Napoli, 80131, Italy Becton Dickinson Italia S.p.A, Via Enrico Cialdini 16, Milano, 20161, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53643, author={Marchiori MF, Riul TB, Oliveira Bortot L, Andrade P, Junqueira GG, Foca G, Doti N, Ruvo M, Dias-baruffi M, Carvalho I, Campo VL}, title={Binding of triazole-linked galactosyl arylsulfonamides to galectin-3 affects Trypanosoma cruzi cell invasion}, date={2017 Nov 1}, journal={Bioorg Med Chem (ISSN: 0968-0896, 1464-3391, 0968-0896linking)}, year={2017}, fullvolume={872}, volume={872}, pages={6049--6059}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030665122&doi=10.1016%2fj.bmc.2017.09.042&partnerID=40&md5=a5352919f051a8299dbc5b2d546a60fc}, abstract={The synthesis of the O-3 triazole-linked galactosyl arylsulfonamides 1–7 as potential inhibitors of Trypanosoma cruzi cell invasion is described. These target compounds were synthesized by Cu(I)-catalysed azide-alkyne cycloaddition reaction (‘click chemistry’) between different azide arylsulfonamides and the alkyne-based sugar 3-O-propynyl-βGalOMe. Inhibition assays of T. cruzi cell invasion with compounds 1–7 showed reduced values of infection index (∼20) for compounds 3 and 5, bearing the corresponding 5-methylisoxazole and 2,4-dimethoxypyrimidine groups, which also presented higher binding affinities to galectin-3 (EC50 17–18 μM) in Corning Epic label-free assays. In agreement with experimental results, the assessment of the theoretical binding of compounds 1–7 to galectin-3 by MM/PBSA method displayed higher affinities for compounds 3 (−9.7 kcal/mol) and 5 (−11.1 kcal/mol). Overall, these achievements highlight compounds 3 and 5 as potential T. cruzi cell invasion blockers by means of a galectin-3 binding-related mechanism, revealing galectin-3 as an important host target for design of novel anti-trypanosomal agents. © 2017 Elsevier Ltd}, keywords={Animals, Binding Sites, Drug Effects, Dose-Response Relationship, Enzyme Inhibitors, Chemical Synthesis, Chemistry, Pharmacology, Fibroblasts, Parasitology, Galactose, Galectin 3, Metabolism, Glycoproteins, Antagonists, Haplorhini, Humans, Molecular Structure, Neuraminidase, Structure-Activity Relationship, Sulfonamides, Triazoles, Trypanocidal Agents, Trypanosoma Cruzi, Enzymology, Cell Invasion, Galactosyl Arylsulfonamides, Trans-Sialidase, Click Chemistry, “click Chemistry”, 3 Triazole Linked Galactosyl Arylsulfonamide Derivative, Antiprotozoal Agent, Methyl 3 O Methyl N [(benzenesulfa Ortho Pyridine) 1h 1, 3 Triazol 4 Yl]beta Dextro Galactopyranoside, Methyl 3 O Methyl N [[(4 Methylpyrimidin 2 Yl)benzenesulfonamide] 1h 1, 6 Dimethoxylpyrimidin 4 Yl)benzenesulfonamide] 1h 1, 6 Dimethylpyrimidin 2 Yl)benzenesulfonamide] 1h 1, Methyl 3 O Methyl N [[(5 Methylisoxazol 3 Yl)benzenesulfonamide] 1h 1, Methyl 3 O Methyl N [[[(phenyl)sulfonyl]acetamide] 1h 1, Methyl 3 O Methyl[(4 Benzenesulfonamide) 1h 1, Pyridoxal 5 Phosphate, Unclassified Drug, Antitrypanosomal Agent, Triazole Derivative, Article, Binding Affinity, Chagas Disease, Controlled Study, Cycloaddition, Drug Protein Binding, Drug Structure, Drug Synthesis, Molecular Mechanics, Protein Targeting, Antagonists And Inhibitors, Chemical Structure, Dose Response, Structure Activity Relation, }, references={(2017), http://www.who.int/mediacentre/factsheets/fs340/en/, Chagas Disease,fact sheet, WHO. 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Am Chem Soc, 127, pp. 1737-1743 Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J.L., Dror, R.O., Shaw, D.E. Improved side-chain torsion potentials for the Amber ff99SB protein force field (2010) Proteins Struct Funct Bioinf, 78, pp. 1950-1958 Wang, J., Wolf, R.M., Caldwell, J.W., Kollman, P.A., Case, D.A., Development and testing of a general amber force field (2004) J Comp Chem, 25, pp. 1157-1174}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Faculty of Pharmaceutical Sciences of Ribeirao Preto - USP, Av. do Cafe S/N, CEP 14040-903 Ribeirao Preto, SP, Brazil., Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, I-80134 Napoli Italy., Faculty of Pharmaceutical Sciences of Ribeirao Preto - USP, Av. do Cafe S/N, CEP 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: vlcampo@fcfrp.usp.br., }, ibbaffiliation={1}, } @article{IBB_ID_11816, author={Ruvo M, Sandomenico A, Tudisco L, De Falco S}, title={Branched peptides for the modulation of protein-protein interactions: More arms are better than one?}, date={2011 Jun}, journal={Curr Med Chem (ISSN: 0929-8673, 1875-533x, 1875-533xelectronic)}, year={2011}, fullvolume={490}, volume={490}, pages={2429--2437}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79957946154&partnerID=40&md5=217b1041fdbe4141be5b25db8e55c835}, abstract={Combinatorial peptide libraries from synthetic or biological sources have been largely used in the last two-decades with the aim of identifying bioactive peptides that specifically bind proteins and modulate their interactions with other protein partners. Differently from biological libraries, synthetic methods allow the development of different kinds of libraries based on two main characteristics: i) the use of building blocks and chemical bonds different from those naturally occurring and ii) the possibility of designing scaffolds with non-linear shapes, as cyclic and branched structures. These two features, alone or in combination, have increased the chemical and structural diversity of peptide libraries expanding the offer of collections for the screenings. Here we describe our and other experiences with branched peptides and the results obtained in the last fifteen years. These clearly indicate how the use of short multimerized peptides can represent a successful approach for different applications ranging from affinity chromatography to the modulation of protein-protein interactions in different biological contexts. © 2011 Bentham Science Publishers Ltd.}, keywords={Combinatorial Peptide Library, Cripto, Fc Receptor, Hepatitis B Virus, Immunoglobulin Purification, Interleukin-6, Map (mulptiple Antigen Peptide), Multimeric Peptides, Neurotensin, Pam (protein A Mimetic), Squamous Cell Carcinoma Antigen 1, Tnfα, Vegfr-1, Growth Factor, Growth Factor Receptor, Protein A Mimetic Peptide, Tripeptide, Unclassified Drug, Vasculotropin Receptor 1, Affinity Chromatography, Amino Acid Sequence, Angiogenesis, Article, Binding Affinity, Cell Differentiation, Cell Fate, Embryonic Stem Cell, Nonhuman, Protein Multimerization, Protein Protein Interaction, Protein Stability, Protein Structure, Systemic Lupus Erythematosus, Animals, Combinatorial Chemistry Techniques, Molecular Structure, Oligopeptides, Protein Binding, }, references={Schnur, D.M., Beno, B.R., Tebben, A.J., Cavallaro, C., Methods for combinatorial and parallel library design (2010) Methods. 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S., Hall, V., Soulet, D., Brundin, P., Critical issues of clinical human embryonic stem cell therapy for brain repair (2008) Trends Neurosci., 31 (3), pp. 146-153 Boheler, K. R., Crider, D. G., Tarasova, Y., Maltsev, V. A., Cardiomyocytes derived from embryonic stem cells (2005) Methods Mol. Med., 108, pp. 417-435 Parish, C. L., Parisi, S., Persico, M. G., Arenas, E., Minchiotti, G., Cripto as a target for improving embryonic stem cell-based therapy in Parkinson's disease (2005) Stem Cells, 23 (4), pp. 471-476. , DOI 10. 1634/stemcells. 2004-0294 Shepard, C. W., Simard, E. P., Finelli, L., Fiore, A. E., Bell, B. P., Hepatitis B virus infection: Epidemiology and vaccination (2006) Epidemiologic Reviews, 28 (1), pp. 112-125. , DOI 10. 1093/epirev/mxj009}, document_type={Journal Article, }, affiliation={Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone, 16, 80134, Napoli, Italy Angiogenesis Lab, Institute of Genetics and Biophysic Adriano Buzzati-Traverso, CNR, Via Pietro Castellino, 111, 80131 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_50197, author={Tornatore L, Sandomenico A, Raimondo D, Low C, Rocci A, Tralau-Stewart C, Capece D, D'Andrea D, Bua M, Boyle E, van Duin M, Zoppoli P, Jaxa-Chamiec A, Thotakura AK, Dyson J, Walker BA, Leonardi A, Chambery A, Driessen C, Sonneveld P, Morgan G, Palumbo A, Tramontano  A, Rahemtulla A, Ruvo M, Franzoso G}, title={Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors}, date={2014 Oct 13}, journal={Cancer Cell (ISSN: 1535-6108)}, year={2014}, fullvolume={586}, volume={586}, pages={495--508}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84919467733&partnerID=40&md5=a983ee9b35919e6f41ea176e7849daea}, abstract={Constitutive NF-kappaB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-kappaB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-kappaB-regulated antiapoptotic factor GADD45beta and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45beta/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-kappaB pathway is possible and, at least for myeloma patients, promises a profound benefit.}, keywords={Antineoplastic Agent, Bortezomib, D Tripeptide Dtp3, Growth Arrest And Dna Damage Inducible Protein 45 Beta Inhibitor, Immunoglobulin Enhancer Binding Protein, Jnk Kinase Mkk7, Jnk Kinase Mkk7 Inhibitor, Protein Inhibitor, Stress Activated Protein Kinase Inhibitor, Tripeptide Derivative, Unclassified Drug, Cell Cycle Protein, Gadd45a Protein, Human, Map2k7 Protein, Mitogen Activated Protein Kinase Kinase 7, Nuclear Protein, Animal Experiment, Animal Model, Antineoplastic Activity, Cancer Cell, Controlled Study, Human Cell, In Vitro Study, Mouse, Multiple Myeloma, Nonhuman, Protein Expression, Protein Protein Interaction, Signal Transduction, Survival Factor, Tumor Xenograft, Antagonists And Inhibitors, Bioavailability, Metabolism, Pathology, Biological Availability, Map Kinase Kinase 7, Nf-Kappa B, Antineoplastic Agents Pharmacokinetics Pharmacology, Cell Cycle Proteins Antagonists, Map Kinase Kinase 7 Antagonists, Multiple Myeloma Metabolism Pathology, Nf-Kappa B Metabolism, Nuclear Proteins Antagonists, }, references={Annunziata, C.M., Davis, R.E., Demchenko, Y., Bellamy, W., Gabrea, A., Zhan, F., Lenz, G., Xiao, W., Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma (2007) Cancer Cell, 12, pp. 115-13 Bjorklund, C.C., Ma, W., Wang, Z.Q., Davis, R.E., Kuhn, D.J., Kornblau, S.M., Wang, M., Orlowski, R.Z., Evidence of a role for activation of Wnt/beta-catenin signaling in the resistance of plasma cells to lenalidomide (2011) J.Biol. 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Gov'T, }, affiliation={Department of Medicine, Centre for Cell Signalling and Inflammation, Imperial College LondonLondon, United Kingdom Institute of Biostructures and Bioimages, National Research Council and CIRPeBNaples, Italy Department of Physics, Sapienza UniversityRome, Italy Drug Discovery Centre, Imperial College LondonLondon, United Kingdom Division of Hematology, University of Torino, AOU San Giovanni BattistaTurin, Italy Section of Haemato-Oncology, The Institute of Cancer ResearchLondon, United Kingdom Department of Hematology, Erasmus University Medical CenterCA Rotterdam, Netherlands Institute for Cancer Genetics, Columbia University Medical CenterNew York, NY, United States Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico IINaples, Italy Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, Second University of NaplesCaserta, Italy IRCCS MultimedicaMilan, Italy Department of Oncology/Hematology, Kantonsspital St. GallenSt. Gallen, Switzerland Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza UniversityRome, Italy IRCCS Multimedica, 20138 Milan, Italy. }, ibbaffiliation={1}, } @article{IBB_ID_9400, author={Marasco D, Saporito A, Ponticelli S, Chambery A, De Falco S, Pedone C, Minchiotti G, Ruvo M}, title={Chemical synthesis of mouse Cripto CFC variants}, date={2006 Sep 15}, journal={Proteins (ISSN: 0887-3585, 1097-0134, 1097-0134electronic)}, year={2006}, fullvolume={345}, volume={345}, pages={779--788}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33746268430&partnerID=40&md5=7147d6457567ed4e3ecaf6636e995c83}, abstract={We report for the first time the chemical synthesis of refolded CFC domain of mouse Cripto (mCFC) and of two variants bearing mutations on residues W107 and H104 involved in Alk4 binding. The domains undergo spontaneous and quantitative refolding in about 4 h, yet with very different kinetics. Disulfide linkages have been assessed by enzyme digestion and mass spectrometry analysis of resulting fragments, and the first experimental studies on structural organization have been conducted by circular dichroism spectroscopy under different pH conditions. Upon refolding, the domains considerably change their conformations, although they do not assume canonical structures, and become highly resistant to enzyme degradation. A comparative study of receptor binding shows that the CFC domain can bind Alk4 and confirms the importance of W107 and H104 for receptor recognition.}, keywords={Cd Spectroscopy, Domain Refolding, Enzyme Digestion, Peptide Synthesis, Receptor Binding, Growth Factor, Protein Cripto, Unclassified Drug, Article, Circular Dichroism, Conformational Transition, Molecular Recognition, Mouse, Nonhuman, Priority Journal, Protein Domain, Protein Synthesis, Activin Receptors, Type I, Amino Acid Sequence, Animals, Binding Sites, Chromatography, Liquid, Epidermal Growth Factor, Kinetics, Mass Spectrometry, Membrane Glycoproteins, Models, Molecular Sequence Data, Mutation, Neoplasm Proteins, Protein Binding, Protein Folding, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, }, references={Dono, R., Scalera, L., Pacifico, F., Acampora, D., Persico, M.G., Simeone, A., The murine cripto gene: Expression during mesoderm induction and early heart morphogenesis (1993) Development, 118, pp. 1157-116 Adamson, E.D., Minchiotti, G., Salomon, D.S., Cripto: A tumor growth factor and more (2002) J Cell Biol, 190, pp. 267-278 Bianco, C., Normanno, N., Salomon, D.S., Ciardiello, F., Role of the cripto (EGF-CFC) family in embryogenesis and cancer (2004) Growth Factors, 22, pp. 133-139 Minchiotti, G., Nodal-dependent Cripto signaling in ES cells: From stem cells to tumor biology (2005) Oncogene, 24, pp. 5668-5675 Wechselberger, C., Strizzi, L., Kenney, N., Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma (2005) Oncogene, 24, pp. 4094-4105 Minchiotti, G., Parisi, S., Liguori, G., Membrane-anchorage of Cripto protein by glycosylphosphatidylinositol and its distribution during early mouse development (2000) Mech Dev, 90, pp. 133-142 Lohmeyer, M., Harrison, P.M., Kannan, S., Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human cripto (1997) Biochemistry, 36, pp. 3837-3845 Salomon, D.S., Bianco, C., Ebert, A.D., The EGF-CFC family: Novel epidermal growth factor-related proteins in development and cancer (2000) Endocr Relat Cancer, 7, pp. 199-226 Foley, S.F., Van Vlijmen, H.W., Boynton, R.E., The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. 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Scope and applications (1991) J Am Chem Soc, 113, pp. 6657-6662 Moroney, J.V., Fullmer, C.S., McCarty, R.E., Characterization of the cysteinyl-containing peptides of the gamma subunit of coupling factor 1 (1984) J Biol Chem, 259, pp. 7281-7285 Adamson, E. D., Minchiotti, G., Salomon, D. S., Cripto: A tumor growth factor and more (2002) J Cell Biol, 190, pp. 267-278 Salomon, D. S., Bianco, C., Ebert, A. D., The EGF-CFC family: Novel epidermal growth factor-related proteins in development and cancer (2000) Endocr Relat Cancer, 7, pp. 199-226 Foley, S. F., Van Vlijmen, H. W., Boynton, R. E., The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis (2003) Eur J Biochem, 270, pp. 3610-3618 Yeo, C. Y., Whitman, M., Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms (2001) Mol Cell, 7, pp. 949-957 Shen, M. M., Schier, A. F., The EGF-CFC gene family in vertebrate development (2000) Trends Genet, 16, pp. 303-309 Xing, P. X., Hu, X. F., Pietersz, G. A., Hosick, H. L., McKenzie, I. F. C., Cripto: A novel target for antibody-based cancer immunotherapy (2004) Cancer Res, 64, pp. 4018-4023 Herrington, E. E., Ram, T. G., Salomon, D. S., Expression of epidermal growth factor-related proteins in the aged adult mouse mammary gland and their relationship to tumorigenesis (1997) J Cell Physiol, 170, pp. 47-56 Kenney, N. J., Smith, G. H., Maroulakou, I. G., Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice (1996) Mol Carcinog, 15, pp. 44-56 Adkins, H. B., Bianco, C., Schiffer, S. G., Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo (2003) J Clin Invest, 112, pp. 575-587 Gray, P. C., Harrison, C. A., Vale, W., Cripto forms a complex with activin and type II activin receptors and can block activin signaling (2003) Proc Natl Acad Sci USA, 100, pp. 5193-5198 Persico, M. G., Liguori, G. L., Parisi, S., D'Andrea, D., Salomon, D. S., Minchiotti, G., Cripto in tumors and embryo development (2001) Biochim Biophys Acta, 1552, pp. 87-93 Song, J., Oh, S. P., Schrewe, H., The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice (1999) Dev Biol, 213, pp. 157-169 Schier, A. F., Shen, M. M., Nodal signalling in vertebrate development (2000) Nature, 403, pp. 385-389 Schiffer, S. G., Foley, S., Kaffashan, A., Fucosylation of Cripto is required for its ability to facilitate nodal signaling (2001) J Biol Chem, 276, pp. 37769-37778 Barcellos-Hoff, M. H., Ewan, K. B., Transforming growth factor-beta and breast cancer: Mammary gland development (2000) Breast Cancer Res, 2, pp. 92-99 Risbridger, G. P., Schmitt, J. F., Robertson, D. M., Activins and inhibins in endocrine and other tumors (2001) Endocr Rev, 22, pp. 836-858 Wakefield, L. M., Roberts, A. B., TGF-beta signaling: Positive and negative effects on tumorigenesis (2002) Curr Opin Genet Dev, 12, pp. 22-29 Harrison, C. A., Gray, P. C., Vale, W. W., Robertson, D. M., Antagonists of activin signaling: Mechanisms and potential biological applications (2005) Trends Endocrinol Metab, 16, pp. 73-78 Cheng, S. K., Olale, F., Bennett, J. T., Brivanlou, A. H., Schier, A. F., EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 (2003) Gene Dev, 17, pp. 31-36 Johnson Jr., W. C., Protein secondary structure and circular dichroism: A practical guide (1990) Proteins, 7, pp. 205-214 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Tam, J. P., Wu, C. R., Liu, W., Zhang, J. W., Bisulfide bond formation in peptides by dimethyl sulfoxide. Scope and applications (1991) J Am Chem Soc, 113, pp. 6657-6662 Moroney, J. V., Fullmer, C. S., McCarty, R. E., Characterization of the cysteinyl-containing peptides of the gamma subunit of coupling factor 1 (1984) J Biol Chem, 259, pp. 7281-7285}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini del CNR, Sezione Biostrutture, Napoli, Italy Istituto di Genetica e Biofisica Adriano B. Traverso del CNR, Napoli, Italy Facoltà di Scienze MMFFNN, Seconda Università di Napoli, Caserta, Italy Facolt di Scienze MMFFNN, Seconda Universit di Napoli, Caserta, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52351, author={Marasco D, Saporito A, Patriarca E, Fasulo R, Spasiano A, Pedone C, Benedetti E, Ruvo M}, title={Chemical synthesis of the of Gstl protein by an NCL method on a X-Met site}, date={2005}, journal={Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print)}, year={2005}, fullvolume={279}, volume={279}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_53864, author={Tornatore L, Capece D, D'Andrea D, Begalli F, Verzella D, Bennett J, Acton G, Campbell EA, Kelly J, Tarbit M, Adams N, Bannoo S, Leonardi A, Sandomenico A, Raimondo D, Ruvo M, Chambery A, Oblak M, Al-obaidi MJ, Kaczmarski RS, Gabriel I, Oakervee HE, Kaiser MF, Wechalekar A, Benjamin R, Apperley JF, Auner HW, Franzoso G}, title={Clinical proof of concept for a safe and effective NF-kappaB-targeting strategy in multiple myeloma}, date={2018 Sep 26}, journal={Br J Haematol (ISSN: 1365-2141electronic, 0007-1048linking)}, year={2018}, fullvolume={223}, volume={223}, pages={N/D--N/D}, url={}, abstract={}, keywords={Nf-Kappab, Apoptosis, Clinical Trials, Drug, Multiple Myeloma, }, references={}, document_type={Letter, }, affiliation={CCSI, Department of Medicine, Imperial College London, London, UK., Cancer Research UK Centre for Drug Development, London, UK., C&C Management Consulting Ltd, Exmouth, UK., Alpha Preclinical Consultancy, Halifax, UK., Independent Consultant, Royston, UK., In2Phase Ltd, Welwyn Garden City, UK., Department of Molecular Medicine, University of Naples Federico II, Naples, Italy., IBB-CNR and CIRPeB, "Federico II" University of Naples, Naples, Italy., Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., DiSTABiF, University of Campania "Luigi Vanvitelli", Caserta, Italy., West Middlesex University Hospital, Isleworth, Greater London, UK., Haematology Department, Chelsea and Westminster Hospital, London, UK., London Haematology Limited, London, UK., Barts Cancer Centre, St Bartholomew's Hospital London, London, UK., Division of Molecular Pathology, The Institute of Cancer Research, London, UK., Royal Free London NHS Foundation Trust, London, UK., Department of Haematology, King's College Hospital, London, UK., Centre for Haematology, Imperial College London, London, UK., Cancer Cell Protein Metabolism, Department of Medicine, Imperial College London, London, UK., }, ibbaffiliation={1}, } @article{IBB_ID_10962, author={De Falco S, Ruvoletto MG, Verdoliva A, Ruvo M, Raucci A, Marino M, Senatore S, Cassani G, Alberti A, Pontisso P, Fassina G}, title={Cloning and Expression of a Novel Hepatitis B Virus-binding Protein from HepG2 Cells}, date={2001 Sep 28}, journal={Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking)}, year={2001}, fullvolume={585}, volume={585}, pages={36613--36623}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035965306&partnerID=40&md5=1e4ad8a82ea9a03ca1f18e41739082b3}, abstract={A direct involvement of the hepatitis B virus (HBV) preS1-(21-47) sequence in virus attachment to cell membrane receptor(s) and the presence on the plasma membranes of HepG2 cells of protein(s) with receptor activity for HBV have been suggested by many previous experiments. In this study, by using a tetravalent derivative of the preS1-(21-47) sequence, we have isolated by affinity chromatography from detergent-solubilized HepG2 plasma membranes a 44-kDa protein (HBV-binding protein; HBV-BP), which was found to closely correspond to the human squamous cell carcinoma antigen 1 (SCCA1), a member of the ovalbumin family of serine protease inhibitors. Comparison of SCCA1 sequence with the sequence of the corresponding HBV-BP cDNA, cloned by polymerase chain reaction starting from RNA poly(A) + fractions extracted from HepG2 cells, indicated the presence of only four nucleotide substitutions in the coding region, leading to three amino acid changes. Intact recombinant HBV-BP lacked inhibitory activity for serine proteases such as α-chymotrypsin and trypsin but inhibited with high potency cysteine proteases such as papain and cathepsin L. Direct binding experiments confirmed the interaction of recombinant HBV-BP with the HBV preS1 domain. HepG2 cells overexpressing HBV-BP after transfection of corresponding cDNA showed a virus binding capacity increased by 2 orders of magnitude compared with untransfected cells, while Chinese hamster ovary cells, which normally do not bind to HBV, acquired susceptibility to HBV binding after transfection. Native HBV particle entry was enhanced in transfected cells. Both recombinant HBV-BP and antibodies to recombinant HBV-BP blocked virus binding and internalization in transfected cells as well as in primary human hepatocytes in a dose-dependent manner. Our findings suggest that this protein plays a major role in HBV infection.}, keywords={Amino Acids, Cell Membranes, Cloning, Viruses, Plasma Membranes, Proteins, Cathepsin L, Chymotrypsin A, Cysteine Proteinase, Nucleotide, Papain, Protein Pres1, Squamous Cell Carcinoma Antigen, Unclassified Drug, Virus Protein, Complementary Dna, Hepatitis B Virus Binding Protein, Human, Hepatitis B Virus-Binding Protein, Polyadenylic Acid, Proteinase Inhibitor, Recombinant Protein, Serine Proteinase Inhibitor, Squamous Cell Carcinoma Related Antigen, Squamous Cell Carcinoma-Related Antigen, Tumor Antigen, Virus Receptor, Amino Acid Substitution, Animal Cell, Article, Cho Cell, Concentration Response, Controlled Study, Enzyme Inhibition, Gene Overexpression, Genetic Transfection, Human Cell, Molecular Cloning, Nonhuman, Polymerase Chain Reaction, Priority Journal, Protein Domain, Protein Expression, Protein Isolation, Receptor Intrinsic Activity, Virus Adsorption, Virus Cell Interaction, Virus Particle, Amino Acid Sequence, Binding Competition, Biosynthesis, Cell Culture, Cell Line, Chemistry, Chromatography, Dose Response, Drug Antagonism, Hamster, Kinetics, Liver Cell, Metabolism, Molecular Genetics, Nucleotide Sequence, Protein Binding, Protein Tertiary Structure, Sequence Homology, Cricetinae, Cricetulus Griseus, Dna Viruses, Neoplasm, Base Sequence, Cysteine Endopeptidases, Dose-Response Relationship, Hepatocytes, Molecular Sequence Data, Protease Inhibitors, Protein Structure, Serpins, Time Factors, Tumor Cells, }, references={Ganem, D., Varmus, H.E., (1987) Annu. 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Acad. Sci., 25, pp. 37-47 Breiner, K. M., Urban, S., Shaller, H., (1998) J. Virol., 72, pp. 8098-8104}, document_type={Journal Article, }, affiliation={TECNOGEN S.C.p.A., Parco Scientifico, Piana M. Verna (CE), Caserta 81015, Italy Universita degli Studi di Padova, Dipto. di Med. Clin. e Sperimentale, Clinica Medica 5, 35128 Padova, Italy TECNOGEN S. C. p. A., Parco Scientifico, Piana M. Verna (CE), Caserta 81015, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53948, author={Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L}, title={Combined HAT/EZH2 modulation leads to cancer-selective cell death}, date={2018 May 22}, journal={Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking)}, year={2018}, fullvolume={261}, volume={261}, pages={25630--25646}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047400725&doi=10.18632%2foncotarget.25428&partnerID=40&md5=e9b8063a2138e7677611200f98cd20f1}, abstract={Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro, ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2. Even aggressive models of cancer, such as p53-/- or TET2-/- cells, responded to MC2884, suggesting MC2884 therapeutic potential also for the therapy of TP53 or TET2-deficient human cancers. MC2884 induced massive apoptosis in ex vivo human primary leukemia blasts with poor prognosis in vivo, by targeting BCL2 expression. MC2884-treatment reduced acetylation of the BCL2 promoter at higher level than combined p300 and EZH2 inhibition. This suggests a key role for BCL-2 reduction in potentiating responsiveness, also in combination therapy with BCL2 inhibitors. Finally, we identified both the mechanism of MC2884 action as well as a potential therapeutic scheme of its use. Altogether, this provides proof of concept for the use of epi-drugs coupled with epigenome analyses to 'personalize' precision medicine. © Petraglia et al.}, keywords={Acetylation, Apoptosis, Cancer, Epigenetics, Methylation, Antineoplastic Agent, Caspase, Mc 2884, Transcription Factor Ezh2, Unclassified Drug, Acute Myeloid Leukemia, Animal Experiment, Animal Model, Antineoplastic Activity, Antiproliferative Activity, Article, Cancer Cell, Cell Cycle, Cell Death, Cell Growth, Cell Migration, Cell Proliferation, Colon Carcinoma, Controlled Study, Cytotoxicity, Drug Effect, Drug Efficacy, Drug Mechanism, Drug Response, Drug Structure, Human, Human Cell, Mouse, Nonhuman, Tumor Volume, Tumor Xenograft, }, references={Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia (2013) N Engl J Med, 368, pp. 2059-2074. , https://doi.org/10.1056/NEJMoa130168 Weinstein, J.N., Collisson, E.A., Mills, G.B., Shaw, K.R., Ozenberger, B.A., Ellrott, K., Shmulevich, I., Stuart, J.M., The Cancer Genome Atlas Pan-Cancer analysis project (2013) Nat Genet, 45, pp. 1113-1120. , https://doi.org/10.1038/ng.2764 Sun, X.J., Man, N., Tan, Y., Nimer, S.D., Wang, L., The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis (2015) Front Oncol, 5, p. 108. , https://doi.org/10.3389/fonc.2015.00108 Avvakumov, N., Cote, J., The MYST family of histone acetyltransferases and their intimate links to cancer (2007) Oncogene, 26, pp. 5395-5407. , https://doi.org/10.1038/sj.onc.1210608 Greer, E.L., Shi, Y., Histone methylation: a dynamic mark in health, disease and inheritance (2012) Nat Rev Genet, 13, pp. 343-357. , https://doi.org/10.1038/nrg3173 Falkenberg, K.J., Johnstone, R.W., Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders (2014) Nat Rev Drug Discov, 13, pp. 673-691. , https://doi.org/10.1038/nrd4360 Parry, L., Clarke, A.R., The Roles of the Methyl-CpG Binding Proteins in Cancer (2011) Genes Cancer, 2, pp. 618-630. , https://doi.org/10.1177/1947601911418499 Muller, S., Filippakopoulos, P., Knapp, S., Bromodomains as therapeutic targets (2011) Expert Rev Mol Med, 13. , https://doi.org/10.1017/S1462399411001992 Kolla, V., Zhuang, T., Higashi, M., Naraparaju, K., Brodeur, G.M., Role of CHD5 in human cancers: 10 years later (2014) Cancer Res, 74, pp. 652-658. , https://doi.org/10.1158/0008-5472.CAN-13-3056 Jariwala, N., Rajasekaran, D., Srivastava, J., Gredler, R., Akiel, M.A., Robertson, C.L., Emdad, L., Sarkar, D., Role of the staphylococcal nuclease and tudor domain containing 1 in oncogenesis (review) (2015) Int J Oncol, 46, pp. 465-473. , https://doi.org/10.3892/ijo.2014.2766 Musselman, C.A., Kutateladze, T.G., PHD fingers: epigenetic effectors and potential drug targets (2009) Mol Interv, 9, pp. 314-323. , https://doi.org/10.1124/mi.9.6.7 Conte, M., Altucci, L., Molecular pathways: the complexity of the epigenome in cancer and recent clinical advances (2012) Clin Cancer Res, 18, pp. 5526-5534. , https://doi.org/10.1158/1078-0432.CCR-12-2037 You, J.S., Jones, P.A., Cancer genetics and epigenetics: two sides of the same coin? 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document_type={Journal Article, }, affiliation={Dipartimento di Medicina di Precisione, Universita degli Studi della Campania Luigi Vanvitelli, Napoli 80138, Italy., Department of Molecular Biology, Radboud University, HB Nijmegen 6500, The Netherlands., IRCCS SDN, Napoli 80143, Italy., Dipartimento di Chimica e Tecnologie del Farmaco 'Sapienza' Universita, Roma 00185, Italy., Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Universita della Campania 'Luigi Vanvitelli', Caserta 81100, Italy., Ospedale Umberto I, Nocera Inferiore 84014, Italy., Istituto di Genetica e Biofisica, Napoli 80131, Italy., Centro Nacional de Analisis Genomico, Barcelona, Spain., Istituto di Biostrutture e Bioimmagini, Napoli, Italy., Department of Hematology, University of Groningen and University Medical Center Groningen, RB Groningen 9700, The Netherlands., European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom., Max Planck Institute for Molecular Genetics, Berlin, Germany., Institute Gustave Roussy, Equipe labellisee Ligue Nationale contre le Cancer (LNCC), Universtite Paris-Saclay, INSERM U1170, Paris, France., Dipartimento di Farmacia, Universita di Napoli 'Federico II', Napoli 80131, Italy., Dipartimento di Farmacia, Universita degli Studi di Salerno, Fisciano I-84084, Italy., Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Roma 00185, Italy., IRCCS SDN, Napoli, 80143, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11311, author={Calvanese L, Sandomenico A, Caporale A, Focà A, Focà G, D'Auria G, Falcigno L, Ruvo M}, title={Conformational And Binding Properties Of Nodal Synthetic Fragments}, date={2014}, journal={Journal Of Peptide Science}, year={2014}, fullvolume={253}, volume={253}, pages={nd--nd}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_12429, author={Tizzano B, Marasco D, Benedetti E, De Capua A, Palladino P, Pedone C, Perretta G, Rossi F, Ragone R, Ruvo M}, title={Conformational conversion of prion proteins: Role synthetic PRP 173-195 fibrillogenic peptide}, date={2004}, journal={Peptide Revolution}, year={2004}, fullvolume={318}, volume={318}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_9287, author={Ronga L, Palladino P, Costantini S, Facchiano A, Ruvo M, Benedetti E, Ragone R, Rossi F}, title={Conformational diseases and structure-toxicity relationships: Lessons from prion-derived peptides}, date={2007 Feb}, journal={Curr Protein Pept Sci (ISSN: 1389-2037, 1389-2037linking)}, year={2007}, fullvolume={535}, volume={535}, pages={83--90}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33847296574&partnerID=40&md5=7b79d68467c13d854285e64f32260cbc}, abstract={The physiological form of the prion protein is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. Available evidence suggests that this protein is essential for neuronal integrity in the brain, possibly with a role in copper metabolism and cellular response to oxidative stress. In prion diseases, the benign cellular form of the protein is converted into an insoluble, protease-resistant abnormal scrapie form. This conversion parallels a conformational change of the polypeptide from a predominantly a-helical to a highly P-sheet secondary structure. The scrapie form accumulates in the central nervous system of affected individuals, and its protease-resistant core aggregates into amyloid Fibrils outside the cell. The pathogenesis and molecular basis of the nerve cell loss that accompanies this process are not understood. Limited structural information is available on aggregate formation by this protein as the possible cause of these diseases and on its toxicity. A large amount of structure-activity studies is based on the prion fragment approach, but the resulting information is often difficult to untangle. This overview focuses on the most relevant structural and functional aspects of the prion-induced conformational disease linked to peptides derived from the unstructured N-terminal and globular C-terminal domains.}, keywords={Amyloid, Copper Binding Protein, N-Linked Glycoprotein, Prion Structure, Prion Toxicity, Transmissible Spongiform Encephalopathies, Amyloid Protein, Antibiotic Agent, Metal Ion, Polyamine Derivative, Polyanion, Polyene Antibiotic Agent, Polypeptide, Prion Protein, Proteinase, Tetracycline, Tetrapyrrole Derivative, Alpha Helix, Amino Terminal Sequence, Beta Sheet, Carboxy Terminal Sequence, Cell Function, Central Nervous System Disease, Conformational Transition, Copper Metabolism, Drug Protein Binding, Enzyme Inhibition, Human, Mammal Cell, Metal Binding, Neuropathology, Nonhuman, Oxidative Stress, Prion Disease, Protein Domain, Protein Expression, Protein Secondary Structure, Review, Scrapie, Species Conservation, Structure Activity Relation, Amino Acid Sequence, Animals, Models, Molecular, Molecular Sequence Data, Nerve Degeneration, Protein Conformation, Protein Structure, Tertiary, Thermodynamics, }, references={Carrel, R.W., Lomas, D.A., (1997) Lancet, 350, pp. 134-13 Temussi, P.A., Masino, L., Pastore, A., (2003) EMBO J., 22, pp. 355-361 Blake, C., Serpell, L., (1996) Structure, 4, pp. 989-998 Thompson, A., White, A.R., McLean, C., Masters, C.L., Cappai, R., Barrow, C.J., (2000) J. 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As for other TGF-betas, it triggers the signaling functions through the interaction with the extracellular domains of type I and type II serine/threonine kinase receptors and with the co-receptor Cripto. Recently, we reported the molecular models of Nodal in complex with its type I receptors (ALK4 and ALK7) as well as with Cripto, as obtained by homology modeling and docking simulations. From such models, potential binding epitopes have been identified. To validate such hypotheses, a series of mutated Nodal fragments have been synthesized. These peptide analogs encompass residues 44-67 of the Nodal protein, corresponding to the pre-helix loop and the H3 helix, and reproduce the wild-type sequence or bear some modifications to evaluate the hot-spot role of modified residues in the receptor binding. Here, we show the structural characterization in solution by CD and NMR of the Nodal peptides and the measurement of binding affinity toward Cripto by surface plasmon resonance. Data collected by both conformational analyses and binding measurements suggest a role for Y58 of Nodal in the recognition with Cripto and confirm that previously reported for E49 and E50. Surface plasmon resonance binding assays with recombinant proteins show that Nodal interacts in vitro also with ALK7 and ALK4 and preliminary data, generated using the Nodal synthetic fragments, suggest that Y58 of Nodal may also be involved in the recognition with these protein partners. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd}, keywords={Nmr, Peptides, Nodal, Tgf-Beta, Alanine Derivative, Cripto Membrane Protein, Epitope, Glutamic Acid, Peptide Fragment, Protein Nodal, Protein Serine Threonine Kinase, Protein Serine Threonine Kinase Alk4, Recombinant Protein, Synthetic Peptide, Unclassified Drug, Article, Binding Affinity, Carboxy Terminal Sequence, Circular Dichroism, Complex Formation, Human, In Vitro Study, Molecular Docking, Molecular Model, Nuclear Overhauser Effect, Priority Journal, Protein Analysis, Protein Conformation, Protein Function, Protein Interaction, Protein Structure, Proton Nuclear Magnetic Resonance, Signal Transduction, Static Electricity, Surface Plasmon Resonance, Wild Type, }, references={Jornvall, H., Reissmann, E., Andersson, O., Mehrkash, M., Ibanez, C.F., ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse (2004) Mol. Cell. 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Biol., 222, pp. 311-333}, document_type={Journal Article, }, affiliation={CIRPeB University of Naples Federico II via Mezzocannone, 16 80134 Napoli Italy Istituto di Biostrutture e Bioimmagini del CNR via Mezzocannone 16, 80134 Napoli Italy Dipartimento di Farmacia University of Naples Federico II via Mezzocannone, 16 80134 Napoli Italy Bioker Multimedica via P. Castellino Napoli 111 Italy CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134, Napoli, Italy. Bioker Multimedica, via P. Castellino, Napoli, Italy 1CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy 2CNR-IBB, via Mezzocannone, 16, 80134 Napoli, Italy 3Dept. of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy. 4Bioker Multimedica, via P. Castellino, 111, Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_8870, author={Guarnieri D, De Capua A, Ventre M, Borzacchiello A, Pedone C, Marasco D, Ruvo M, Netti PA}, title={Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters}, date={2010 Jul}, journal={Acta Biomaterialia (ISSN: 1878-7568, 1742-7061)}, year={2010}, fullvolume={510}, volume={510}, pages={2532--2539}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77955271320&partnerID=40&md5=f5f6f0d04a9b54b33edd5140d834136c}, abstract={Understanding the influence of a controlled spatial distribution of biological cues on cell activities can be useful to design "cell instructive" materials, able to control and guide the formation of engineered tissues in vivo and in vitro. To this purpose, biochemical and mechanical properties of the resulting biomaterial must be carefully designed and controlled. In this work, the effect of covalently immobilized RGD peptide gradients on poly(ethylene glycol) diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device generating gradients based on a fluidic chamber. Cell response to RGD gradients with different slope (0.7, 1 and 2 mM cm(-1)) was qualitatively and quantitatively assessed by evaluating cell adhesion and, in particular, cell migration, compared to cells seeded on hydrogels with uniform distribution of RGD peptides. To evaluate the influence of RGD gradient and to exclude any concentration effect on cell response, all analyses were carried out in a specific region of the gradients which displayed the same average concentration of RGD (1.5 mM). Results suggest that cells recognize the RGD gradient and adhere onto it assuming a stretched shape. Moreover, cells tend to migrate in the direction of the gradient, as their speed is higher than that of cells migrating on hydrogels with a uniform distribution of RGD and increases by increasing RGD gradient steepness. This increment is due to an augmentation of bias speed component of the mean squared speed, that is, the drift of the cell population migrating on the anisotropic surface provided by the RGD gradient. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.}, keywords={Biological Cues, Cell Instructive Materials, Cell Migration, Hydrogels, Signal Gradients, Acrylic Acid Derivative, Arginylglycylaspartic Acid, Biomaterial, Macrogol, Arginyl-Glycyl-Aspartic Acid, Macrogol Derivative, Oligopeptide, Animal Cell, Animal Tissue, Anisotropy, Cell Activity, Cell Adhesion, Cell Function, Cell Population, Controlled Study, Covalent Bond, Immobilized Cell, In Vitro Study, Mouse, Nonhuman, Priority Journal, Qualitative Analysis, Quantitative Analysis, Tissue Engineering, Cell Motion, Chemistry, Cell Movement, Polyethylene Glycols, }, references={Lutolf, M.P., Hubbell, J.A., Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering (2005) Nat. Biotechnol., 23 (1), pp. 47-55. , Revie Sands, R.W., Mooney, D.J., Polymers to direct cell fate by controlling the microenvironment (2007) Curr. Opin. 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Mater., 17, pp. 809-813 Jeon, N.L., Dertinger, S.K.W., Chiu, D.T., Choi, I.S., Stroock, A.D., Whitesides, G.M., Generation of solution and surface gradients using microfluidic systems (2000) Langmuir, 16, pp. 8311-8316 Burdick, J.A., Khademhosseini, A., Langer, R., Fabrication of gradient hydrogels using a microfluidics/ photopolymerization process (2004) Langmuir, 20 (13), pp. 5153-5156 Boyden, S., The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes (1962) J. Exp. Med., 115, pp. 453-466 Nelson, R.D., Quie, P.G., Simmons, R.L., Chemotaxis under agarose: A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leucocytes and monocytes (1975) J. Immunol., 115, pp. 1650-1656 Moghe, P.V., Nelson, R.D., Tranquillo, R.T., Cytokine-stimulated chemotaxis of human neutrophils in a 3-D conjoined fibrin gel assay (1995) J. Immunol. 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Res., 312 (13), pp. 2424-2432 Kipper, M.J., Kleinman, H.K., Wang, F.W., Covalent surface chemistry gradients for presenting bioactive peptides (2007) Anal. Biochem., 363 (2), pp. 175-184 Brandley, B.K., Schnaar, R.L., Tumor cell haptotaxis on covalently immobilized linear and exponential gradients of a cell adhesion peptide (1989) Dev. Biol., 135 (1), pp. 74-86 Mosesson, M.W., Siebenlist, K.R., Meh, D.A., The structure and biological features of fibrinogen and fibrin (2001) Ann. N.Y. Acad. Sci., 936, pp. 11-30 Van Hinsbergh, V.W., Collen, A., Koolwijk, P., Role of the fibrin matrix in angiogenesis (2001) Ann. N.Y. Acad. Sci., 936, pp. 426-437 Hubbell, J.A., Bioactive biomaterials (1999) Curr. Opin. 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Sci., 99, pp. 419-430 Tranquillo, R.T., Chemotactic movement of single cells (1991) ASGSB Bull., 4 (2), pp. 75-85. , Review Sarvestani, A.S., Jabbari, E., Analysis of cell locomotion on ligand gradient substrates (2009) Biotechnol. Bioeng., 103, pp. 424-429 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Dickinson, R.B., Tranquillo, R.T., Optimal estimation of cell movement indices from the statistical analysis of cell tracking data (1993) AIChE J., 39, pp. 1995-2010 Walmod, P.S., Hartmann-Petersen, R., Berezin, A., Prag, S., Kiselyov, V.V., Berezin, V., Evaluation of individual-cell motility (2001) Methods Mol. Biol., 161, pp. 59-83 Mann, B.K., Gobin, A.S., Tsai, A.T., Schmedlen, R.H., West, J.L., Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering (2001) Biomaterials, 22, pp. 3045-3051 Massia, S.P., Hubbell, J.A., An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3 mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation (1991) J. Cell. Biol., 114 (5), pp. 1089-1100 Irvine, D.J., Hue, K.A., Mayes, A.M., Griffith, L.G., Simulations of cell-surface integrin binding to nanoscale-clustered adhesion ligands (2002) Biophys. J., 82, pp. 120-132 Dunn, G.A., Characterising a kinesis response: Time averaged measures of cell speed and directional persistence (1983) Agents Actions Suppl., 12, pp. 14-33 Codling, E.A., Plank, M.J., Benhamou, S., Random walk models in biology (2008) J. R Soc. Interface, 5, pp. 813-834 Di Milla, P.A., Barbee, K., Lauffenburger, D.A., Mathematical model for the effects of adhesion and mechanics on cell migration speed (1991) Biophys. J., 60 (1), pp. 15-37 Maheshwari, G., Lauffenburger, D.A., Deconstructing (and reconstructing) cell migration (1998) Microsc Res. Tech., 43, pp. 358-368 Distasi, C., Ariano, P., Zamburlin, P., Ferraro, M., In vitro analysis of neuron-glial cell interactions during cellular migration (2002) Eur. Biophys. J., 31, pp. 81-88 Lutolf, M. P., Hubbell, J. A., Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering (2005) Nat. Biotechnol., 23 (1), pp. 47-55. , Revie Sands, R. W., Mooney, D. J., Polymers to direct cell fate by controlling the microenvironment (2007) Curr. Opin. Biotechnol., 18 (5), pp. 448-453. , Review Plummer, S. T., Wang, Q., Bohn, P. W., Stockton, R., Schwartz, M. A., Electrochemically derived gradients of the extracellular matrix protein fibronectin on gold (2003) Langmuir, 19, pp. 7528-7536 Adams, D. N., Kao, E. Y. C., Hypolite, C. L., Distefano, M. D., Hu, W. S., Letourneau, P. C., Growth cones turn and migrate up an immobilized gradient of the laminin IKVAV peptide (2005) J. Neurobiol., 62, pp. 134-147 Kang, C. E., Gemeinhart, E. J., Gemeinhart, R. A., Cellular alignment by grafted adhesion peptide surface density gradients (2004) J. Biomed. Mater. Res. A, 71, pp. 403-411 Bhangale, S. M., Tjong, V., Wu, L., Yakovlev, N., Moran, P. M., Biologically active protein gradients via microstamping (2005) Adv. Mater., 17, pp. 809-813 Jeon, N. L., Dertinger, S. K. W., Chiu, D. T., Choi, I. S., Stroock, A. D., Whitesides, G. M., Generation of solution and surface gradients using microfluidic systems (2000) Langmuir, 16, pp. 8311-8316 Burdick, J. A., Khademhosseini, A., Langer, R., Fabrication of gradient hydrogels using a microfluidics/ photopolymerization process (2004) Langmuir, 20 (13), pp. 5153-5156 Nelson, R. D., Quie, P. G., Simmons, R. L., Chemotaxis under agarose: A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leucocytes and monocytes (1975) J. Immunol., 115, pp. 1650-1656 Moghe, P. V., Nelson, R. D., Tranquillo, R. T., Cytokine-stimulated chemotaxis of human neutrophils in a 3-D conjoined fibrin gel assay (1995) J. Immunol. Methods, 180, pp. 193-211 Knapp, D. M., Helou, E. F., Tranquillo, R. T., A fibrin or collagen gel assay for tissue cell chemotaxis: Assessment of fibroblast chemotaxis to RGDSP (1999) Exp. Cell. Res., 247, pp. 543-553 Smith, J. T., Tomfohr, J. K., Wells, M. C., Beebe, T. P., Kepler, T. B., Reichert, W. M., Measurement of cell migration on surface-bound fibronectin gradients (2004) Langmuir, 20, pp. 8279-8286 De Long, S. A., Moon, J. J., West, J. L., Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration (2005) Biomaterials, 26 (16), pp. 3227-3234 De Long, S. A., Gobin, A. S., West, J. L., Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration (2005) Journal of Controlled Release, 109, pp. 139-148 Smith, J. T., Elkin, J. T., Reichert, W. M., Directed cell migration on fibronectin gradients: Effect of gradient slope (2006) Exp. Cell. Res., 312 (13), pp. 2424-2432 Kipper, M. J., Kleinman, H. K., Wang, F. W., Covalent surface chemistry gradients for presenting bioactive peptides (2007) Anal. Biochem., 363 (2), pp. 175-184 Brandley, B. K., Schnaar, R. L., Tumor cell haptotaxis on covalently immobilized linear and exponential gradients of a cell adhesion peptide (1989) Dev. Biol., 135 (1), pp. 74-86 Mosesson, M. W., Siebenlist, K. R., Meh, D. A., The structure and biological features of fibrinogen and fibrin (2001) Ann. N. Y. Acad. Sci., 936, pp. 11-30 Van Hinsbergh, V. W., Collen, A., Koolwijk, P., Role of the fibrin matrix in angiogenesis (2001) Ann. N. Y. Acad. Sci., 936, pp. 426-437 Hubbell, J. A., Bioactive biomaterials (1999) Curr. Opin. Biotechnol., 10 (2), pp. 123-129. , Review Elbert, D. L., Hubbell, J. A., Conjugate addition reactions combined with free-radical cross-linking for the design of materials for tissue engineering (2001) Biomacromolecules, 2 (2), pp. 430-441 Bryant, S. J., Nicodemus, G. D., Villanueva, I., Designing 3D photopolymer hydrogels to regulate biomechanical cues and tissue growth for cartilage tissue engineering (2008) Pharm. Res., 25 (10), pp. 2379-2386 Hern, D. L., Hubbell, J. A., Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing (1998) J. Biomed. Mater. Res., 39, pp. 266-276 Stokes, C. L., Lauffenburger, D. A., Williams, S. K., Migration of individual microvessel endothelial cells: Stochastic model and parameter measurement (1991) J. Cell. Sci., 99, pp. 419-430 Sarvestani, A. S., Jabbari, E., Analysis of cell locomotion on ligand gradient substrates (2009) Biotechnol. Bioeng., 103, pp. 424-429 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Dickinson, R. B., Tranquillo, R. T., Optimal estimation of cell movement indices from the statistical analysis of cell tracking data (1993) AIChE J., 39, pp. 1995-2010 Walmod, P. S., Hartmann-Petersen, R., Berezin, A., Prag, S., Kiselyov, V. V., Berezin, V., Evaluation of individual-cell motility (2001) Methods Mol. Biol., 161, pp. 59-83 Mann, B. K., Gobin, A. S., Tsai, A. T., Schmedlen, R. H., West, J. L., Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering (2001) Biomaterials, 22, pp. 3045-3051 Massia, S. P., Hubbell, J. A., An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3 mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation (1991) J. Cell. Biol., 114 (5), pp. 1089-1100 Irvine, D. J., Hue, K. A., Mayes, A. M., Griffith, L. G., Simulations of cell-surface integrin binding to nanoscale-clustered adhesion ligands (2002) Biophys. J., 82, pp. 120-132 Dunn, G. A., Characterising a kinesis response: Time averaged measures of cell speed and directional persistence (1983) Agents Actions Suppl., 12, pp. 14-33 Codling, E. A., Plank, M. J., Benhamou, S., Random walk models in biology (2008) J. R Soc. Interface, 5, pp. 813-834 Di Milla, P. A., Barbee, K., Lauffenburger, D. A., Mathematical model for the effects of adhesion and mechanics on cell migration speed (1991) Biophys. J., 60 (1), pp. 15-37}, document_type={Journal Article, }, affiliation={Interdisciplinary Research Centre on Biomaterials (CRIB), Naples, Italy. Institute for Biomedical and Composite Materials, CNR, Naples 80125, Italy Institute of Biostructures and Bioimages, CNR, University of Naples Federico II, Naples 80134, Italy Department of Biological Science, Section Biostructures, University of Naples Federico II, via Mezzocannone 16, 80134 Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11861, author={Saporito A, Falcigno L, D'Auria G, Minchiotti G, Marasco D, Benedetti E, Pedone C, Ruvo M}, title={Cripto protein sub-domains: synthesis and structural studies}, date={2005}, journal={Peptides 2004 Proceedings}, year={2005}, fullvolume={288}, volume={288}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_52913, author={Klauzinska M, Bertolette D, Tippireddy S, Strizzi L, Gray PC, Gonzales M, Duroux M, Ruvo M, Wechselberger C, Castro NP, Rangel MC, Focà A, Sandomenico A, Hendrix MJC, Salomon D, Cuttitta F}, title={Cripto-1: an extracellular protein – connecting the sequestered biological dots}, date={2015}, journal={Connect Tissue Res (ISSN: 0300-8207)}, year={2015}, fullvolume={274}, volume={274}, pages={N/D--N/D}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84940497380&partnerID=40&md5=9cf5b5f9f262dd4d4a02842a70774360}, abstract={Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways. In addition, there are several naturally occurring binding partner proteins (BPPs) for CR-1 that can either agonize or antagonize its bioactivity. We will review the collective role of CR-1 as an extracellular protein, discuss caveats to consider in developing a quantitation assay, define possible mechanistic avenues applicable for drug discovery, and report on our experimental approaches to overcome these problematic issues. © 2015 Taylor & Francis Group, LLC.}, keywords={Autoantibodies, Cripto-1, Cripto-1 Detection, Drug Discovery, Inflammation, }, references={}, document_type={, }, affiliation={Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA Department of Pathology, Program in Cancer Biology and Epigenomics, Stanley Manne Children’s Research Institute at Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA Office of Research Operations, Office of the Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA Laboratory of Cancer Biology, Biomedicine Group, Department of Health Science and Technology, Aalborg University, Aalborg East, Denmark CIRPeB, University of Naples Federico II, Napoli, Italy Istituto di Biostrutture e Bioimmagini del CRN, Napoli, Italy Greiner Bio-One Diagnostics GmbH, Rainbach im Mühlkreis, Austria Dipartimento di Farmacia, University of Naples Federico II, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52410, author={Calce E, Sandomenico A, Saviano M, Ruvo M, De Luca S}, title={Cysteine Co-Oxidation Process Driven By Native Peptide Folding: An Example On Her2 Receptor Model System}, date={2014}, journal={Amino Acids (ISSN: 0939-4451, 1438-2199, 1438-2199electronic)}, year={2014}, fullvolume={342}, volume={342}, pages={1197--1206}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84898919459&partnerID=40&md5=431ce3a1a90f0cc3d455e023f5ec0511}, abstract={Synthetic models0of receptors that have relevant0biological roles are valuable tools for studying receptors itself and the corresponding ligands> Their properties can be validated at first by their capacity to fold in solution under native-|ike conditions and to assume co~formations structurally and funstionally equivalent to those in0the native receptor. In this co~text, a new strategy to prepare0the two-fragments synthetic recuptor model HER2-DIVMP, an independent structural and functional0motif of HER2, has been developud and the folding properties have been investigated. The stratewy is based on a one-step cystei~e co-oxidation procedure in sliwhtly alkaline aqueous buffers, whereby the two separate peptide0chains are allowed to self-Asse} ble in solution. Under these co~ditions, the two chains spontaneously form the expected heterodimer with the correct pattern of disulfide bridges. To gain insights on the folding mechanism, wu investigated the folding of two scrambled variants of the constituent peptide chains. 2014 Springer-Verlag Wien}, keywords={Cysteine Co-Oxidation Process, Her2 Receptor, Mass Spectrometry Analysis, Peptide Folding, Receptor Model, Epidermal Growth Factor Receptor 2, Erbb2 Protein, Human, Amino Acid Sequence, Chemistry, Dimerization, Metabolism, Molecular Genetics, Oxidation Reduction Reaction, Protein Folding, Molecular Sequence Data, Oxidation-Reduction, Cysteine Chemistry Metabolism, Erbb-2 Chemistry Metabolism, }, references={Andreu, D., Albericio, F., Sole, N. A., Munson, M. 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D., (2000) Fmoc Solid Phase Peptide Synthesis, A Practical Approach, , Oxford University Press Cary Cho, H. S., Mason, K., Ramyar, K. X., Stanley, A. M., Gabelli, S. B., Denney, D. W., Leahy, D. J., Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab (2003) Nature, 421, pp. 756-760. , 12610629 10. 1038/nature01392 Creighton, T. E., Disulphide bonds and protein stability (1988) BioEssays, 8, pp. 57-63. , 3282505 10. 1002/bies. 950080204 Engebretsen, M., Agner, E., Sandosham, J., Fischer, P. M., Unexpected lability of cysteine acetamidomethyl thiol protecting group. Tyrosine ring alkylation and disulfide bond formation upon acidolysis (1997) J Pept Res, 49, pp. 341-346. , 9176818 10. 1111/j. 1399-3011. 1997. tb01135. x Eritja, R., Ziehler-Martin, J. P., Walker, P. A., Lee, T. D., Legesse, K., Albericio, F., Kaplan, B. 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M., Bulaj, G., Optimization of oxidative folding methods for cysteine-rich peptides: A study of conotoxins containing three disulfide bridges (2011) J Pept Sci, 17, pp. 1-7. , 20814907 10. 1002/psc. 1283 Tam, J. P., Wu, C. R., Liu, W., Zhang, J. W., Disulfide bond formation in peptides by dimethyl sulfoxide. Scope and applications (1991) J Am Chem Soc, 113, pp. 6657-6662. , 10. 1021/ja00017a044 Thornton, J. M., Disulphide bridges in globular proteins (1981) J Mol Biol, 151, pp. 261-287. , 7338898 10. 1016/0022-2836 (81) 90515-5 Wedemeyer, W. J., Welker, E., Narayan, M., Scheraga, H. A., Disulfide bonds and protein folding (2000) Biochemistry, 39, pp. 4207-4216. , 10757967 10. 1021/bi992922o Zhang, S., Lin, F., Hossain, M. A., Shabanpoor, F., Tregear, G. W., Wade, J. D., Simultaneous post-cysteine (S-Acm) group removal quenching of iodine and isolation of peptide by one step ether precipitation (2008) Int J Pept Res Ther, 14, pp. 301-305. , 10. 1007/s10989-008-9148-x}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Institute of Biostructures0and Bioimaging, National Rusearch Council, 80134 Naplus, Italy CIRPeB, Via Mezzocannone 16, 80134 Naples, Italy Institute of Crystallography, National Research Council, Via Amendola 122/O, 70126 Bari, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54449, author={Nawaz MI, Rezzola S, Tobia C, Coltrini D, Belleri M, Mitola S, Corsini M, Sandomenico A, Caporale A, Ruvo M, Presta M}, title={D-Peptide analogues of Boc-Phe-Leu-Phe-Leu-Phe-COOH induce neovascularization via endothelial N-formyl peptide receptor}, date={2020 Aug}, journal={Angiogenesis (ISSN: 0969-6970linking)}, year={2020}, fullvolume={51}, volume={51}, pages={357--369}, url={}, abstract={N-formyl peptide receptors (FPRs) are G protein-coupled receptors involved in the recruitment and activation of immune cells in response to pathogen-associated molecular patterns. Three FPRs have been identified in humans (FPR1-FPR3), characterized by different ligand properties, biological function and cellular distribution. Recent findings from our laboratory have shown that the peptide BOC-FLFLF (L-BOC2), related to the FPR antagonist BOC2, acts as an angiogenesis inhibitor by binding to various angiogenic growth factors, including vascular endothelial growth factor-A(165) (VEGF). Here we show that the all-D-enantiomer of L-BOC2 (D-BOC2) is devoid of any VEGF antagonist activity. At variance, D-BOC2, as well as the D-FLFLF and succinimidyl (Succ)-D-FLFLF (D-Succ-F3) D-peptide variants, is endowed with a pro-angiogenic potential. In particular, the D-peptide D-Succ-F3 exerts a pro-angiogenic activity in a variety of in vitro assays on human umbilical vein endothelial cells (HUVECs) and in ex vivo and in vivo assays in chick and zebrafish embryos and adult mice. This activity is related to the capacity of D-Succ-F3 to bind FRP3 expressed by HUVECs. Indeed, the effects exerted by D-Succ-F3 on HUVECs are fully suppressed by the G protein-coupled receptor inhibitor pertussis toxin, the FPR2/FPR3 antagonist WRW4 and by an anti-FPR3 antibody. A similar inhibition was observed following WRW4-induced FPR3 desensitization in HUVECs. Finally, D-Succ-F3 prevented the binding of the anti-FPR3 antibody to the cell surface of HUVECs. In conclusion, our data demonstrate that the angiogenic activity of D-Succ-F3 is due to the engagement and activation of FPR3 expressed by endothelial cells, thus shedding a new light on the biological function of this chemoattractant receptor.}, keywords={Angiogenesis, Boc2, D-Peptide, Formyl Peptide Receptor, Huvecs, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Department of Ophthalmology, King Saud University, Riyadh, Kingdom of Saudi Arabia. Istituto Di Biostrutture e Bioimmagini, CNR, Napoli, Italy. Istituto Di Cristallografia, CNR, Trieste, Italy. AnBition srl, Napoli, Italy. Italian Consortium for Biotechnology (CIB), Unit of Brescia, Trieste, Italy. marco.presta@unibs.it.}, ibbaffiliation={1}, } @article{IBB_ID_10967, author={Tamburino R, Severino V, Sandomenico A, Ruvo M, Parente A, Chambery A, Di Maro A}, title={De novo sequencing and characterization of a novel Bowman-Birk inhibitor from Lathyrus sativus L. seeds by electrospray mass spectrometry}, date={2012 Oct 30}, journal={Mol Biosyst (ISSN: 1742-206x, 1742-2051linking, 1742-2051electronic)}, year={2012}, fullvolume={353}, volume={353}, pages={3232--3241}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84868109268&partnerID=40&md5=7afa2d32bd0a5e3d645241760bf492a5}, abstract={Bowman-Birk serine protease inhibitors (BBIs) from legume seeds are small proteins showing a two-head structure with distinct reactive site loops, which inhibit two molecules of the same enzyme or two different proteases. Purification and characterization of new BBIs is of broad interest for understanding the basic molecular mechanisms underlying natural defence against the action of proteolytic enzymes. In this study, two novel acidic BBIs (LSI-1a and LSI-2a) were isolated from L. sativus seeds using classical biochemical techniques and characterized for their inhibitory activity. In addition, the N-terminal sequencing of LSI-1a was performed by Edman degradation up to residue 10 and the complete primary structure of the most abundant form (LSI-2a) was determined by using a combination of mass spectrometry approaches, including MALDI-TOF MS, tandem MS and Electron Transfer Dissociation coupled with Proton Transfer Reaction (ETD/PTR) top-down sequencing of N- and C-termini. Furthermore, the LSI-2a dimerization surface has also been investigated by a combination of gel filtration, electrophoretic techniques and homology modelling. Knowing the structure of small proteins inhibiting proteolytic enzymes is of general importance for understanding the defence mechanisms against degradation for their use in biological applications as well as for designing artificial inhibitors.}, keywords={Lathyrus Sativus, Bowman Birk Inhibitor, Trypsin Inhibitor, Vegetable Protein, Amino Acid Sequence, Article, Chemical Structure, Chemistry, Genetics, Isolation And Purification, Mass Spectrometry, Metabolism, Molecular Genetics, Plant Seed, Sequence Alignment, Sequence Analysis, Models, Molecular Sequence Data, Plant Proteins, Matrix-Assisted Laser Desorption-Ionization, Bowman-Birk Soybean, Pharmacology, }, references={Birk, Y., (2003) Plant Protease Inhibitors: Significance in Nutrition, Plant Protection, Cancer Prevention and Genetic Engineering, , Springer-Verlag, Berlin Heidelberg New Yor Laskowski Jr., M., Kato, I., (1980) Annu. Rev. Biochem., 49, pp. 593-626 Birk, Y., (1985) Int. J. Pept. 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BioSyst., 7, pp. 2500-2507 De Azevedo Pereira, R., Valencia-Jimenez, A., Magalhaes, C.P., Prates, M.V., Melo, J.A., De Lima, L.M., De Sales, M.P., Grossi-De-Sa, M.F., (2007) J. Agric. Food Chem., 55, pp. 10714-10719 Falco, M.F., Silva-Filho, M.C., (2003) Plant Physiol. Biochem., 41, pp. 761-766 Fang, E.F., Hassanien, A.A., Wong, J.H., Bah, C.S., Soliman, S.S., Ng, T.B., (2010) J. Agric. Food Chem., 58, pp. 10729-10735 Ye, X.Y., Ng, T.B., Rao, P.F., (2001) Biochem. Biophys. Res. Commun., 289, pp. 91-96 Kennedy, A.R., (1998) Am. J. Clin. Nutr., 68, pp. 1406S-1412S Weder, J.K., Hinkers, S.C., (2004) J. Agric. Food Chem., 52, pp. 4219-4226 Scarafoni, A., Consonni, A., Galbusera, V., Negri, A., Tedeschi, G., Rasmussen, P., Magni, C., Duranti, M., (2008) Phytochemistry, 69, pp. 1820-1825 Clemente, A., Moreno, F.J., Marin-Manzano Mdel, C., Jimenez, E., Domoney, C., (2010) Mol. Nutr. 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Biol., 9, p. 35 Zhou, H., Zhou, Y., (2002) Protein Sci., 11, pp. 2714-2726 Coon, J.J., Syka, J.E., Shabanowitz, J., Hunt, D.F., (2005) Biotechniques, 38, p. 519. , 521, 523 Mikesh, L.M., Ueberheide, B., Chi, A., Coon, J.J., Syka, J.E., Shabanowitz, J., Hunt, D.F., (2006) Biochim. Biophys. Acta, 1764, pp. 1811-1822 Syka, J.E., Coon, J.J., Schroeder, M.J., Shabanowitz, J., Hunt, D.F., (2004) Proc. Natl. Acad. Sci. U. S. A., 101, pp. 9528-9533 Ramasarma, P.R., Appu Rao, A.G., Rao, D.R., (1994) J. Agric. Food Chem., 42, pp. 2139-2146 Chambery, A., Pisante, M., Di Maro, A., Di Zazzo, E., Ruvo, M., Costantini, S., Colonna, G., Parente, A., (2007) Proteins, 67, pp. 209-218}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, I-81100 Caserta, Italy Institute of Biostructures and Bioimaging-IBB, CNR, I-80134, Napoli, Italy Institute of Crystallography, CNR, I-70126, Bari, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10974, author={Zatelli MC, Tagliati F, Di Ruvo M, Castermans E, Cavazzini L, Daly AF, Ambrosio MR, Beckers A, degli Uberti E}, title={Deletion of exons 1-3 of the MEN1 gene in a large Italian family causes the loss of menin expression}, date={2014 Jun}, journal={Fam Cancer (ISSN: 1389-9600)}, year={2014}, fullvolume={406}, volume={406}, pages={273--280}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84903277879&partnerID=40&md5=bcf0a05162f977360238ceee1db077f6}, abstract={Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to inactivating mutations of the MEN1 gene (chromosome 11q13). MEN1 mutations are mainly represented by nonsense, deletions/insertions, splice site or missense mutations that can be detected by direct sequencing of genomic DNA. However, MEN1 patients with large heterozygous deletions may escape classical genetic screening and may be misidentified as phenocopies, thereby hindering proper clinical surveillance. We employed a real-time polymerase chain reaction application, the TaqMan copy number variation assay, to evaluate a family in which we failed to identify an MEN1 mutation by direct sequencing, despite a clear clinical diagnosis of MEN1 syndrome. Using the TaqMan copy number variation assay we identified a large deletion of the MEN1 gene involving exons 1 and 2, in three affected family members, but not in the other nine family members that were to date clinically unaffected. The same genetic alteration was not found in a group of ten unaffected subjects, without family history of endocrine tumors. The MEN1 deletion was further confirmed by multiplex ligation-dependent probe amplification, which showed the deletion extended from exon 1 to exon 3. This new approach allowed us to correctly genetically diagnose three clinical MEN1 patients that were previously considered as MEN1 phenocopies. More importantly, we excluded the presence of genetic alterations in the unaffected family members. These results underline the importance of using a variety of available biotechnology approaches when pursuing a genetic diagnosis in a clinically suggestive setting of inherited endocrine cancer. © 2014 Springer Science+Business Media.}, keywords={Gene Deletions, Genetic Analysis, Men1, Mlpa, Quantitative Pcr, Menin Protein, Tumor Protein, Unclassified Drug, Adult, Aged, Article, Case Report, Controlled Study, Copy Number Variation, Exon, Familial Cancer, Female, Gene Function, Gene Mutation, Human, Human Tissue, Middle Aged, Multiple Endocrine Neoplasia, Multiple Endocrine Neoplasia Type 1 Gene, Multiplex Ligation Dependent Probe Amplification, Phenotype, Priority Journal, Protein Depletion, Protein Expression, Real Time Polymerase Chain Reaction, Sequence Analysis, Tumor Gene, Young Adult, }, references={Thakker, R.V., Newey, P.J., Walls, G.V., Bilezikian, J., Dralle, H., Ebeling, P.R., Melmed, S., Brandi, M.L., Endocrine society clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1) (2012) J Clin Endocrinol Metab, 97, pp. 2990-3011. , doi:10.1210/jc.2012-123 Thakker, R.V., Multiple endocrine neoplasia type 1 (MEN1) (2010) Best Pract Res Clin Endocrinol Metab, 24, pp. 355-370. , doi:10.4103/2230-8210.104058 Falchetti, A., Brandi, M.L., Multiple endocrine neoplasia type I variants and phenocopies: More than a nosological issue? (2009) J Clin Endocrinol Metab, 94, pp. 1518-1520. , doi:10.1210/jc.2009-0494 Sakurai, A., Suzuki, S., Kosugi, S., Okamoto, T., Uchino, S., Miya, A., Imai, T., Yamazaki, M., Multiple endocrine neoplasia type 1 in Japan: Establishment and analysis of a multicentre database (2012) Clin Endocrinol (Oxf), 76, pp. 533-539. , doi:10.1111/j.1365-2265.2011.04227.x MEN Consortium of Japan Lemos, M.C., Thakker, R.V., Multiple endocrine neoplasia type 1 (MEN1): Analysis of 1336 mutations reported in the first decade following identification of the gene (2008) Hum Mutat, 29, pp. 22-32. , doi:10.1002/humu.20605 Tham, E., Grandell, U., Lindgren, E., Toss, G., Skogseid, B., Nordenskjold, M., Clinical testing for mutations in the MEN1 gene in Sweden: A report on 200 unrelated cases (2007) Journal of Clinical Endocrinology and Metabolism, 92 (9), pp. 3389-3395. , http://jcem.endojournals.org/cgi/reprint/92/9/3389, DOI 10.1210/jc.2007-0476 Jager, A.C., Friis-Hansen, L., Hansen, T.V., Eskildsen, P.C., Solling, K., Knigge, U., Hansen, C.P., Nielsen, F.C., Characteristics of the Danish families with multiple endocrine neoplasia type 1 (2006) Mol Cell Endocrinol, 249, pp. 123-132. , doi:10.1016/j.mce.2006.02.008 Karges, W., Jostarndt, K., Maier, S., Flemming, A., Weitz, M., Wissmann, A., Feldmann, B., Boehm, B.O., Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region (2000) Journal of Endocrinology, 166 (1), pp. 1-9 Giraud, S., Zhang, C.X., Serova-Sinilnikova, O., Wautot, V., Salandre, J., Buisson, N., Waterlot, C., Calender, A., Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders (1998) American Journal of Human Genetics, 63 (2), pp. 455-467. , DOI 10.1086/301953 Owens, M., Ellard, S., Vaidya, B., Analysis of gross deletions in the MEN1 gene in patients with multiple endocrine neoplasia type 1 (2008) Clinical Endocrinology, 68 (3), pp. 350-354. , DOI 10.1111/j.1365-2265.2007.03045.x Ellard, S., Multiple endocrine neoplasia types 1 and 2 (2004) Methods Mol Med, 92, pp. 267-283 Kong, C., Ellard, S., Johnston, C., Farid, N.R., Multiple endocrine neoplasia type 1Burin from Mauritius: A novel MEN 1 mutation (2001) Journal of Endocrinological Investigation, 24 (10), pp. 806-810 Zatelli, M.C., Trasforini, G., Leoni, S., Frigato, G., Buratto, M., Tagliati, F., Rossi, R., Degli Uberti, E.C., BRAF V600E mutation analysis increases diagnostic accuracy for papillary thyroid carcinoma in fine-needle aspiration biopsies (2009) Eur J Endocrinol, 161, pp. 467-473. , doi:10.1530/EJE-09-0353 Alvelos, M.I., Vinagre, J., Fonseca, E., Barbosa, E., Teixeira-Gomes, J., Sobrinho-Simões, M., Soares, P., MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism (2012) Eur J Endocrinol, 168, pp. 119-128. , doi:10.1530/EJE-12-0327 Zatelli, M.C., Piccin, D., Bottoni, A., Ambrosio, M.R., Margutti, A., Padovani, R., Scanarini, M., Degli, U.E.C., Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin A secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro (2004) Journal of Clinical Endocrinology and Metabolism, 89 (10), pp. 5181-5188. , DOI 10.1210/jc.2003-031954 Kishi, M., Tsukada, T., Shimizu, S., Futami, H., Ito, Y., Kanbe, M., Obara, T., Yamaguchi, K., A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1 (1998) Japanese Journal of Cancer Research, 89 (1), pp. 1-5 Bergman, L., Boothroyd, C., Palmer, J., Grimmond, S., Walters, M., Teh, B., Shepherd, J., Hayward, N., Identification of somatic mutations of the MEN1 gene in sporadic endocrine tumours (2000) Br J Cancer, 83, pp. 1003-1008 Cavaco, B.M., Domingues, R., Bacelar, M.C., Cardoso, H., Barros, L., Gomes, L., Ruas, M.M.A., Leite, V., Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions (2002) Clinical Endocrinology, 56 (4), pp. 465-473. , DOI 10.1046/j.1365-2265.2002.01505.x Verges, B., Boureille, F., Goudet, P., Murat, A., Beckers, A., Sassolas, G., Cougard, P., Calender, A., Pituitary disease in MEN type 1 (MEN1): Data from the France-Belgium MEN1 multicenter study (2002) Journal of Clinical Endocrinology and Metabolism, 87 (2), pp. 457-465. , DOI 10.1210/jc.87.2.457 Cebrian, A., Ruiz-Llorente, S., Cascon, A., Pollan, M., Diez, J.J., Pico, A., Telleria, D., Robledo, M., Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients (2003) J Med Genet, 40, pp. e72 Kikuchi, M., Ohkura, N., Yamaguchi, K., Obara, T., Tsukada, T., Gene dose mapping delineated boundaries of a large germline deletion responsible for multiple endocrine neoplasia type 1 (2004) Cancer Letters, 208 (1), pp. 81-88. , DOI 10.1016/j.canlet.2003.10.011, PII S0304383503007092 Lairmore, T.C., Piersall, L.D., DeBenedetti, M.K., Dilley, W.G., Mutch, M.G., Whelan, A.J., Zehnbauer, B., Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1) (2004) Ann Surg, 239, pp. 637-645. , doi:10.1097/01.sla.0000124383.98416.8d Fukuuchi, A., Nagamura, Y., Yaguchi, H., Ohkura, N., Obara, T., Tsukada, T., A whole MEN1 gene deletion flanked by Alu repeats in a family with multiple endocrine neoplasia type 1 (2006) Jpn J Clin Oncol, 36, pp. 739-744. , doi:10.1093/jjco/hyl089 Cosme, A., Alvarez, M., Beguiristain, A., Cobo, A.M., Robledo, M., Aranzadi, M.J., Ojeda, E., Goikoetxea, U., Clinical and molecular features in a family with multiple endocrine neoplasia type-1 syndrome (2008) J Gastroenterol Hepatol, 31, pp. 637-642. , doi:10.1016/S0210-5705(08)75811-4 Bergman, L., Teh, B., Cardinal, J., Palmer, J., Walters, M., Shepherd, J., Cameron, D., Hayward, N., Identification of MEN1 gene mutations in families with MEN 1 and related disorders (2000) Br J Cancer, 83, pp. 1009-1014 Thevenon, J., Bourredjem, A., Faivre, L., Cardot-Bauters, C., Calender, A., Murat, A., Giraud, S., Goudet, P., Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: A Groupe d'etude des Tumeurs Endocrines (GTE) cohort study (2013) Hum Mol Genet, 22, pp. 1940-1948. , doi:10.1093/hmg/ddt039 Thakker, R. V., Newey, P. J., Walls, G. V., Bilezikian, J., Dralle, H., Ebeling, P. R., Melmed, S., Brandi, M. L., Endocrine society clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1) (2012) J Clin Endocrinol Metab, 97, pp. 2990-3011. , doi: 10. 1210/jc. 2012-123 Thakker, R. V., Multiple endocrine neoplasia type 1 (MEN1) (2010) Best Pract Res Clin Endocrinol Metab, 24, pp. 355-370. , doi: 10. 4103/2230-8210. 104058 Lemos, M. C., Thakker, R. V., Multiple endocrine neoplasia type 1 (MEN1): Analysis of 1336 mutations reported in the first decade following identification of the gene (2008) Hum Mutat, 29, pp. 22-32. , doi: 10. 1002/humu. 20605 Jager, A. C., Friis-Hansen, L., Hansen, T. V., Eskildsen, P. C., Solling, K., Knigge, U., Hansen, C. P., Nielsen, F. C., Characteristics of the Danish families with multiple endocrine neoplasia type 1 (2006) Mol Cell Endocrinol, 249, pp. 123-132. , doi: 10. 1016/j. mce. 2006. 02. 008 Zatelli, M. C., Trasforini, G., Leoni, S., Frigato, G., Buratto, M., Tagliati, F., Rossi, R., Degli Uberti, E. C., BRAF V600E mutation analysis increases diagnostic accuracy for papillary thyroid carcinoma in fine-needle aspiration biopsies (2009) Eur J Endocrinol, 161, pp. 467-473. , doi: 10. 1530/EJE-09-0353 Alvelos, M. I., Vinagre, J., Fonseca, E., Barbosa, E., Teixeira-Gomes, J., Sobrinho-Sim es, M., Soares, P., MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism (2012) Eur J Endocrinol, 168, pp. 119-128. , doi: 10. 1530/EJE-12-0327 Zatelli, M. C., Piccin, D., Bottoni, A., Ambrosio, M. R., Margutti, A., Padovani, R., Scanarini, M., Degli, U. E. C., Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin A secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro (2004) Journal of Clinical Endocrinology and Metabolism, 89 (10), pp. 5181-5188. , DOI 10. 1210/jc. 2003-031954 Cavaco, B. M., Domingues, R., Bacelar, M. C., Cardoso, H., Barros, L., Gomes, L., Ruas, M. M. A., Leite, V., Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions (2002) Clinical Endocrinology, 56 (4), pp. 465-473. , DOI 10. 1046/j. 1365-2265. 2002. 01505. x Lairmore, T. C., Piersall, L. D., DeBenedetti, M. K., Dilley, W. G., Mutch, M. G., Whelan, A. J., Zehnbauer, B., Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1) (2004) Ann Surg, 239, pp. 637-645. , doi: 10. 1097/01. sla. 0000124383. 98416. 8d}, document_type={Journal Article, }, affiliation={Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy LTTA, University of Ferrara, Via Fossato di Mortara 70, 44100 Ferrara, Italy Department of Clinical Genetics, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium Section of Pathology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11637, author={Guarnieri D, Borzacchiello A, De Capua A, Marasco D, Ruvo M, Netti PA}, title={Dependence of cell migration parameters on steepness of RGD gradient slope}, date={2008}, journal={World Biomater Congr (ISSN: 9781-6156)}, year={2008}, fullvolume={344}, volume={344}, pages={271--271}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84869040361&partnerID=40&md5=0abf60aa65d7cb39cb8adc0406631698}, abstract={}, keywords={, }, references={Martin, P., (1997) Science, 276, p. 7 De Long, S.A., Gobin, A.S., West, J.L., (2005) J Control Release, 109, p. 139 Griffith, L.G., (2002) Ann NY Acad Sci, 961, pp. 83-95 Hubbell, J.A.Z., (1999) Tissue Engineering of Vascular Prosthetic Grafts, p. 561. , Austin: RG Landes Company Stokes, C.L., Lauffenburger, D.A., Williams, S.K., (1991) J Cell Sci., 99, p. 419 De Long, S. A., Gobin, A. S., West, J. L., (2005) J Control Release, 109, p. 139 Griffith, L. G., (2002) Ann NY Acad Sci, 961, pp. 83-95 Hubbell, J. A. Z., (1999) Tissue Engineering of Vascular Prosthetic Grafts, p. 561. , Austin: RG Landes Company Stokes, C. L., Lauffenburger, D. A., Williams, S. K., (1991) J Cell Sci., 99, p. 419}, document_type={Abstract, Conference, }, affiliation={Interdisciplinary Research Centre of Biomedical Materials (CRIB), University of Naples Federico II, P.le Tecchio 80, 80125 Naples, Italy Istituto di Biostrutture e Bioimmagini Del CNR, via Mezzocannone, 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54798, author={Russo L, Mascanzoni F, Farina B, Dolga AM, Monti A, Caporale A, Culmsee C, Fattorusso R, Ruvo M, Doti N}, title={Design, Optimization, and Structural Characterization of an Apoptosis-Inducing Factor Peptide Targeting Human Cyclophilin A to Inhibit Apoptosis Inducing Factor-Mediated Cell Death}, date={2021 Aug 12}, journal={J Med Chem (ISSN: 0022-2623linking)}, year={2021}, fullvolume={3}, volume={3}, pages={11445--11459}, url={}, abstract={Blocking the interaction between the apoptosis-inducing factor (AIF) and cyclophilin A (CypA) by the AIF fragment AIF(370-394) is protective against glutamate-induced neuronal cell death and brain injury in mice. Starting from AIF(370-394), we report the generation of the disulfide-bridged and shorter variant AIF(381-389) and its structural characterization by nuclear magnetic resonance (NMR) in the free and CypA-bound state. AIF(381-389) in both the free and bound states assumes a β-hairpin conformation similar to that of the fragment in the AIF protein and shows a highly reduced conformational flexibility. This peptide displays a similar in vitro affinity for CypA, an improved antiapoptotic activity in cells and an enhanced proteolytic stability compared to the parent peptide. The NMR-based 3D model of the AIF(381-389)/CypA complex provides a better understanding of the binding hot spots on both the peptide and the protein and can be exploited to design AIF/CypA inhibitors with improved pharmacokinetic and pharmacodynamics features.}, keywords={Animals , Apoptosis Drug Effects , Apoptosis Inducing Factor Chemical Synthesis Chemistry Pharmacology , Brain Injuries Drug Therapy , Cell Death Drug Effects , Cell Survival Drug Effects , Cultured , Cyclophilin A Antagonists, Inhibitors Metabolism , Dose-Response Relationship, Drug Design , Glutamic Acid Metabolism , Humans , Molecular Structure , Structure-Activity Relationship}, references={}, document_type={Journal Article}, affiliation={Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli", Via Vivaldi 43, 81100 Caserta, Italy. Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone, 16, 80134 Napoli, Italy. Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany. Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), Research School of Behavioural and Cognitive Neurosciences (BCN), Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands.}, ibbaffiliation={1}, } @article{IBB_ID_54455, author={Monti A, Sturlese M, Caporale A, Roger JA, Mascanzoni F, Ruvo M, Doti N}, title={Design, synthesis, structural analysis and biochemical studies of stapled AIF(370-394) analogues as ligand of CypA}, date={2020 Dec}, journal={Bba-Gen Subjects (ISSN: 0304-4165linking, 0005-2728, 0006-3002print)}, year={2020}, fullvolume={72}, volume={72}, pages={129717--129717}, url={}, abstract={BACKGROUND: The neuronal apoptotic process requires the nuclear translocation of Apoptosis Inducing Factor (AIF) in complex with Cyclophilin A (CypA) with consequent chromatin condensation and DNA degradation events. Targeting CypA by delivering an AIF-blocking peptide (AIF(370-394)) provides a significant neuroprotection, demonstrating the biological relevance of the AIF/CypA complex. To date pharmaceutical compounds targeting this complex are missing. METHODS: We designed and synthesized a set of mono and bicyclic AIF(370-394) analogs containing both disulfide and 1,2,3-triazole bridges, in the attempt to both stabilize the peptide conformation and improve its binding affinity to CypA. Peptide structures in solution and in complex with CypA have been studied by circular dichroism (CD), Nuclear Magnetic Resonance (NMR) and molecular modeling. The ability of stapled peptides to interact with CypA was evaluated by using Epic Corning label free technique and Isothermal Titration Calorimetry experiments. RESULTS: We identified a stapled peptide analogue of AIF(370-394) with a ten-fold improved affinity for CypA. Molecular modeling studies reveal that the new peptide acquires β-turn/β-fold structures and shares with the parent molecule the same binding region on CypA. CONCLUSIONS: Data obtained provide invaluable assistance in designing new ligand of CypA for therapeutic approaches in neurodegenerative diseases. GENERAL SIGNIFICANCE: Due to the crucial role of AIF/CypA complex formation in neurodegeneration, identification of selective inhibitors is of high importance for targeted therapies. We describe new bicyclic peptide inhibitors with improved affinity for CypA, investigating the kinetic, thermodynamic and structural effects of conformational constraints on the protein-ligand interaction, and their utility for drug design.}, keywords={Apoptosis Inducing Factor Chemistry Metabolism, Cyclophilin A Metabolism, Drug Design, Humans, Ligands, Molecular Docking Simulation, Neuroprotective Agents Chemical Synthesis Chemistry Pharmacology, Peptides Chemical Synthesis Chemistry Pharmacology, Aif(370–394) Stapled Peptide, Aif Cypa Complex, Circular Dichroism (cd), Click Chemistry, Enspire Label Free, Isothermal Titration Calorimetry (itc), Nmr And Molecular Modeling Analysis, }, references={}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone, 16, 80134 Napoli, Italy DISTABIF, Università degli Studi della Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, CE, Italy. Molecular Modeling Section, Dipartimento di Scienze del Farmaco, Università di Padova, via F. Marzolo 5, 35131 Padova, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54445, author={Cusano AM, Aliberti A, Cusano A, Ruvo M}, title={Detection of small DNA fragments by biolayer interferometry}, date={2020 Oct 15}, journal={Anal Biochem (ISSN: 0003-2697linking, 1096-0309electronic)}, year={2020}, fullvolume={64}, volume={64}, pages={113898--113898}, url={}, abstract={Small molecular weight species such as miRNAs and other nucleic acid fragments are gaining an increased interest as biomarkers for relevant diseases. Also, cheap and rapid assays for their routine detection are becoming an urgent need. We have investigated the usability and convenience of a price affordable, label free and fast technique for their detection on a laboratory scale small device based on Bio-Layer Interferometry. Using a model DNA fragment (7 kDa), we have found that the technique is effectively fast and sensitive enough for the detection of nucleic acid fragments having a MW below the stated molecular size detection limit (10 kDa). The test molecule has been detected in solution at 100 nM in a direct capture experiment and up to about 10 nM following an improved approach where an enhancing probe is used to increase the apparent molecular dimensions of the analyte. The technique, following further optimizations, can be applied for the routine, cheap and fast analysis of small nucleic acid fragments that have a relevance in diagnosis and in therapy.}, keywords={Biolayer Interferometry, Biosensors, Molecular Quantification, Small Dna Hybridization Sensor, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Cerict Scarl, Italy. Electronic address: angelamaria.cusano@cerict.it. Dipartimento di Ingegneria, Università Del Sannio, Italy. Istituto di Biostrutture e Bioimmagini, CNR, Italy. Electronic address: menotti.ruvo@unina.it.}, ibbaffiliation={1}, } @article{IBB_ID_54773, author={Sivaccumar JP, Leonardi A, Iaccarino E, Corvino G, Sanguigno L, Chambery A, Russo R, Valletta M, Latino D, Capasso D, Doti N, Ruvo M, Sandomenico A}, title={Development of a New Highly Selective Monoclonal Antibody against Preferentially Expressed Antigen in Melanoma (PRAME) and Identification of the Target Epitope by Bio-Layer Interferometry}, date={2021 Mar 20}, journal={Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596)}, year={2021}, fullvolume={9}, volume={9}, pages={N/D--N/D}, url={}, abstract={BACKGROUND: Monoclonal antibodies (mAbs) against cancer biomarkers are key reagents in diagnosis and therapy. One such relevant biomarker is a preferentially expressed antigen in melanoma (PRAME) that is selectively expressed in many tumors. Knowing mAb's epitope is of utmost importance for understanding the potential activity and therapeutic prospective of the reagents. METHODS: We generated a mAb against PRAME immunizing mice with PRAME fragment 161-415; the affinity of the antibody for the protein was evaluated by ELISA and SPR, and its ability to detect the protein in cells was probed by cytofluorimetry and Western blotting experiments. The antibody epitope was identified immobilizing the mAb on bio-layer interferometry (BLI) sensor chip, capturing protein fragments obtained following trypsin digestion and performing mass spectrometry analyses. RESULTS: A mAb against PRAME with an affinity of 35 pM was obtained and characterized. Its epitope on PRAME was localized on residues 202-212, taking advantage of the low volumes and lack of fluidics underlying the BLI settings. CONCLUSIONS: The new anti-PRAME mAb recognizes the folded protein on the surface of cell membranes suggesting that the antibody's epitope is well exposed. BLI sensor chips can be used to identify antibody epitopes.}, keywords={Animals, Antibodies, Monoclonal Chemistry Immunology Pharmacology, Antibody Specificity, Antigens, Neoplasm Immunology, Antineoplastic Agents, Immunological Chemistry Immunology Pharmacology, Dose-Response Relationship, Drug, Drug Development, Enzyme-Linked Immunosorbent Assay, Epitopes Chemistry Immunology, Flow Cytometry, Humans, Interferometry, Kinetics, Melanoma, Molecular Targeted Therapy, Protein Binding Immunology, Recombinant Proteins, Spectrometry, Matrix-Assisted Laser Desorption-Ionization, Prame, Bio-Layer Interferometry, Epitope Identification, Mice}, references={}, document_type={Journal Article}, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80142 Napoli, Italy. Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche (DISTABIF), Università L. Vanvitelli, 80100 Caserta, Italy. Centro di Servizio di Ateneo per le Scienze e Tecnologie per la Vita (CESTEV), Università di Napoli Federico II, 80145 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54133, author={Foca G, Iaccarino E, Foca A, Sanguigno L, Untiveros G, Cuevas-nunez M, Strizzi L, Leonardi A, Ruvo M, Sandomenico A}, title={Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro}, date={2019 Mar}, journal={Biochimie (ISSN: 0300-9084linking, 1638-6183electronic)}, year={2019}, fullvolume={515}, volume={515}, pages={246--256}, url={}, abstract={Human Cripto-1 (Cripto-1), the founding member of the EGF-CFC superfamily, is a key regulator of many processes during embryonic development and oncogenesis. Cripto-1 is barely present or even absent in normal adult tissues while it is aberrantly re-expressed in various tumors. Blockade of the CFC domain-mediated Cripto-1 functions is acknowledged as a promising therapeutic intervention point to inhibit the tumorigenic activity of the protein. In this work, we report the generation and characterization of murine monoclonal antibodies raised against the synthetic folded CFC [112-150] domain of the human protein. Through subtractive ELISA assays clones were screened for the ability to specifically recognize "hot spot" residues on the CFC domain, which are crucial for the interaction with Activin Type I receptor (ALK4) and GRP78. On selected antibodies, SPR and epitope mapping studies have confirmed their specificity and have revealed that recognition occurs only on a conformational epitope. Furthermore, FACS analyses have confirmed the ability of 1B4 antibody to recognize the membrane-anchored and soluble native Cripto-1 protein in a panel of human cancer cells. Finally, we have evaluated its functional effects through in vitro cellular signaling assays and cell cycle analysis. These findings suggest that the selected anti-CFC mAbs have the potential to neutralize the protein oncogenic activity and may be used as theranostic molecules suitable as tumor homing agents for Cripto-1-overexpressing cancer cells and tissues and to overcome drug-resistance in routine cancer therapies.}, keywords={Activin Receptors, Type I, Immunology, Metabolism, Animals, Antibodies, Monoclonal, Murine-Derived, Chemistry, Neoplasm, Neutralizing, Cell Line, Tumor, Flow Cytometry, Gpi-Linked Proteins, Heat-Shock Proteins, Humans, Intercellular Signaling Peptides And Proteins, Inbred Balb C, Neoplasm Proteins, Protein Domains, Cancer Biomarker, Cripto-1, Neutralizing Monoclonal Antibodies, Type I Immunology Metabolism , Murine-Derived Chemistry Immunology , Neoplasm Chemistry Immunology , Neutralizing Chemistry Immunology , Gpi-Linked Proteins Immunology Metabolism , Heat-Shock Proteins Immunology Metabolism , Intercellular Signaling Peptides And Proteins Immunology Metabolism , Mice , Neoplasm Proteins Immunology Metabolism, }, references={}, document_type={Journal Article, }, affiliation={Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy., Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy., Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA., Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA; College of Dental Medicine, Dwners Grove, Chicago, IL, USA., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy. Electronic address: menotti.ruvo@unina.it., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy. Electronic address: annamaria.sandomenico@cnr.it., Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy. Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA. College of Dental Medicine, Dwners Grove, Chicago, IL, USA.}, ibbaffiliation={1}, } @article{IBB_ID_50984, author={Scognamiglio PL, Doti N, Grieco P, Pedone C, Ruvo M, Marasco D}, title={Discovery Of Small Peptide Antagonists Of Ped/Pea15-D4alpha Interaction From Simplified Combinatorial Libraries}, date={2011 May}, journal={Chem Biol Drug Des (ISSN: 1747-0277, 1747-0285)}, year={2011}, fullvolume={443}, volume={443}, pages={319--327}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79954618035&partnerID=40&md5=bd71e2be486cbcd993494354f9485d5f}, abstract={Most biological processes involve permanent and temporary interactions between different proteins: protein complexes often play key roles in human diseases and, as a consequence, molecules that prevent protein-protein interactions can be potential new therapeutic agents to treat diseases. Here, we describe a simplified approach by which small synthetic peptide libraries were screened to identify the inhibitors of the complex between phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes15 (PED/PEA15) and D4α, a functional domain of the phospholipase D1, that is involved in the molecular mechanisms of insulin resistance occurring in type 2 diabetes. By using an enzyme-linked immunosorbent assay (ELISA)-based screening, performed on a fully automated platform, we analyzed two simplified peptide libraries in a positional scanning format. This screening led to the identification of small peptides able to inhibit PED/PEA15-D4α interaction. The selection of inhibitors was carried out employing combined competitive and direct experiments, through ELISA and surface plasmon resonance techniques, providing peptides with IC 50 values in the micromolar range. Our results showed that the protein complex PED/PEA15-D4α is susceptible to peptides having H-donor groups and aromatic rings on specific positions. These small sequences can be considered as promising scaffolds that could be converted into higher-affinity inhibitor compounds. By a simplified approach small synthetic peptide libraries were screened to identify inhibitors of the complex between PED/PEA15 and D4α that is involved in molecular mechanisms of insulin resistance in type 2 diabetes. Small peptide sequences having H-donor groups and aromatic rings on specific positions are able to inhibit the complex and are promising scaffolds that could be converted into higher-affinity inhibitor compounds. © 2011 John Wiley & Sons A/S.}, keywords={Competitive Assays, Enzyme-Linked Immunosorbent Assay, Simplified Combinatorial Peptide Libraries, Surface Plasmon Resonance, Glutamylglycylglycyltyrosylaspartylhistidyltyrosine, Glutamylglycylglycyltyrosylprolylhistidyltyrosine, Lysylglycylglycylmethionylalanylmethionylleucine, Lysylglycylglycylserylprolylphenylalanylglutamine, Lysylglycylglycylserylprolylphenylalanyltyrosine, Phospholipase D1, Phospholipase D1 D4 Alpha, Phospholipase D1 Ped, Unclassified Drug, Article, Combinatorial Library, Controlled Study, Enzyme Linked Immunosorbent Assay, Insulin Resistance, Non Insulin Dependent Diabetes Mellitus, Nonhuman, Priority Journal, Protein Interaction, Screening, Automation, Laboratory, Binding, Cloning, Molecular, Combinatorial Chemistry Techniques, Type 2, Escherichia Coli, High-Throughput Screening Assays, Inhibitory Concentration 50, Intracellular Signaling Peptides And Proteins, Kinetics, Phosphoproteins, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Structure-Activity Relationship, }, references={Scior, T., Bernard, P., Medina-Franco, J.L., Maggiora, G.M., Large compound databases for structure-activity relationships studies in drug discovery (2007) Mini Rev Med Chem, 7, pp. 851-86 Frank, R., Heikens, W., Heisterberg-Moutsis, G., Blocker, H., A new general approach for the simultaneous chemical synthesis of large numbers of oligonucleotides: segmental solid supports (1983) Nucleic Acids Res, 11, pp. 4365-4377 Houghten, R.A., General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids (1985) Proc Natl Acad Sci USA, 82, pp. 5131-5135 Balakin, K.V., Kozintsev, A.V., Kiselyov, A.S., Savchuk, N.P., Rational design approaches to chemical libraries for hit identification (2006) Curr Drug Discov Technol, 3, pp. 49-65 Ecker, D.J., Crooke, S.T., Combinatorial drug discovery: which methods will produce the greatest value? (1995) Biotechnology (NY), 13, pp. 351-360 Kennedy, J.P., Williams, L., Bridges, T.M., Daniels, R.N., Weaver, D., Lindsley, C.W., Application of combinatorial chemistry science on modern drug discovery (2008) J Comb Chem, 10, pp. 345-354 Pinilla, C., Appel, J.R., Blanc, P., Houghten, R.A., Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries (1992) BioTechniques, 13, pp. 901-905 Betzi, S., Restouin, A., Opi, S., Arold, S.T., Parrot, I., Guerlesquin, F., Morelli, X., Collette, Y., Protein-protein interaction inhibition (2P2I) combining high throughput and virtual screening: application to the HIV-1 Nef protein (2007) Proc Natl Acad Sci USA, 104, pp. 19256-19261 Wells, J.A., McClendon, C.L., Reaching for high-hanging fruit in drug discovery at protein-protein interfaces (2007) Nature, 450, pp. 1001-1009 Chene, P., Drugs targeting protein-protein interactions (2006) ChemMedChem, 1, pp. 400-411 Shultz, M.D., Ham, Y.W., Lee, S.G., Davis, D.A., Brown, C., Chmielewski, J., Small-molecule dimerization inhibitors of wild-type and mutant HIV protease: a focused library approach (2004) J Am Chem Soc, 126, pp. 9886-9887 Zhao, H.F., Kiyota, T., Chowdhury, S., Purisima, E., Banville, D., Konishi, Y., Shen, S.H., A mammalian genetic system to screen for small molecules capable of disrupting protein-protein interactions (2004) Anal Chem, 76, pp. 2922-2927 Ponticelli, S., Marasco, D., Tarallo, V., Albuquerque, R.J., Mitola, S., Takeda, A., Stassen, J.M., De Falco, S., Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1 (2008) J Biol Chem, 283, pp. 34250-34259 Sillerud, L.O., Larson, R.S., Design and structure of peptide and peptidomimetic antagonists of protein-protein interaction (2005) Curr Protein Pept Sci, 6, pp. 151-169 Martin, E.J., Blaney, J.M., Siani, M.A., Spellmeyer, D.C., Wong, A.K., Moos, W.H., Measuring diversity: experimental design of combinatorial libraries for drug discovery (1995) J Med Chem, 38, pp. 1431-1436 Marasco, D., Perretta, G., Sabatella, M., Ruvo, M., Past and future perspectives of synthetic peptide libraries (2008) Curr Protein Pept Sci, 9, pp. 447-467 He, J., Eckert, R., Pharm, T., Simanian, M.D., Hu, C., Yarbrough, D.K., Qi, F., Shi, W., Novel synthetic antimicrobial peptides against Streptococcus mutans (2007) Antimicrob Agents Chemother, 51, pp. 1351-1358 Condorelli, G., Vigliotta, G., Iavarone, C., Caruso, M., Tocchetti, C.G., Andreozzi, F., Cafieri, A., Beguinot, F., PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus (1998) EMBO J, 17, pp. 3858-3866 Fiory, F., Formisano, P., Perruolo, G., Beguinot, F., Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism (2009) Am J Physiol Endocrinol Metab, 297, pp. E592-E601 Viparelli, F., Cassese, A., Doti, N., Paturzo, F., Marasco, D., Dathan, N.A., Monti, S.M., Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells (2008) J Biol Chem, 283, pp. 21769-21778 Doti, N., Cassese, A., Marasco, D., Paturzo, F., Sabatella, M., Viparelli, F., Dathan, N., Ruvo, M., Residues 762-801 of PLD1 mediate the interaction with PED/PEA15 (2010) Mol Biosyst, 6, pp. 2039-2048 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Geysen, H.M., Rodda, S.J., Mason, T.J., A priori delineation of a peptide which mimics a discontinuous antigenic determinant (1986) Mol Immunol, 23, pp. 709-715 Ruvo, M., Scardino, P., Cassani, G., Fassina, G., Facile manual synthesis of peptide libraries (1994) Protein Pept Lett, 1, pp. 187-192 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors (1991) Anal Biochem, 198, pp. 268-277 Flier, J.S., Insulin receptors and insulin resistance (1983) Annu Rev Med, 34, pp. 145-160 Cheng, A.C., Coleman, R.G., Smyth, K.T., Cao, Q., Soulard, P., Caffrey, D.R., Salzberg, A.C., Huang, E.S., Structure-based maximal affinity model predicts small-molecule druggability (2007) Nat Biotechnol, 25, pp. 71-75 Arkin, M.R., Randal, M., DeLano, W.L., Hyde, J., Luong, T.N., Oslob, J.D., Raphael, D.R., Braisted, A.C., Binding of small molecules to an adaptive protein-protein interface (2003) Proc Natl Acad Sci USA, 100, pp. 1603-1608 Sidhu, S.S., Fairbrother, W.J., Deshayes, K., Exploring protein-protein interactions with phage display (2003) Chembiochem, 4, pp. 14-25 Pillutla, R.C., Hsiao, K.C., Beasley, J.R., Brandt, J., Ostergaard, S., Hansen, P.H., Spetzler, J.C., Goldstein, N.I., Peptides identify the critical hotspots involved in the biological activation of the insulin receptor (2002) J Biol Chem, 277, pp. 22590-22594 Nakamura, G.R., Reynolds, M.E., Chen, Y.M., Starovasnik, M.A., Lowman, H.B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc Natl Acad Sci USA, 99, pp. 1303-1308 Besterman, J.M., Duronio, V., Cuatrecasas, P., Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger (1986) Proc Natl Acad Sci USA, 83, pp. 6785-6789 Sung, T.C., Zhang, Y., Morris, A.J., Frohman, M.A., Structural analysis of human phospholipase D1 (1999) J Biol Chem, 274, pp. 3659-3666 Xie, Z., Ho, W.T., Exton, J., Association of the N- and C-terminal domains of Phospholipase D is required for catalytic activity (1998) J Biol Chem, 273, pp. 34679-34682 Houghten, R. A., General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids (1985) Proc Natl Acad Sci USA, 82, pp. 5131-5135 Balakin, K. V., Kozintsev, A. V., Kiselyov, A. S., Savchuk, N. P., Rational design approaches to chemical libraries for hit identification (2006) Curr Drug Discov Technol, 3, pp. 49-65 Ecker, D. J., Crooke, S. T., Combinatorial drug discovery: which methods will produce the greatest value? (1995) Biotechnology (NY), 13, pp. 351-360 Kennedy, J. P., Williams, L., Bridges, T. M., Daniels, R. N., Weaver, D., Lindsley, C. W., Application of combinatorial chemistry science on modern drug discovery (2008) J Comb Chem, 10, pp. 345-354 Wells, J. A., McClendon, C. L., Reaching for high-hanging fruit in drug discovery at protein-protein interfaces (2007) Nature, 450, pp. 1001-1009 Shultz, M. D., Ham, Y. W., Lee, S. G., Davis, D. A., Brown, C., Chmielewski, J., Small-molecule dimerization inhibitors of wild-type and mutant HIV protease: a focused library approach (2004) J Am Chem Soc, 126, pp. 9886-9887 Zhao, H. F., Kiyota, T., Chowdhury, S., Purisima, E., Banville, D., Konishi, Y., Shen, S. H., A mammalian genetic system to screen for small molecules capable of disrupting protein-protein interactions (2004) Anal Chem, 76, pp. 2922-2927 Sillerud, L. O., Larson, R. S., Design and structure of peptide and peptidomimetic antagonists of protein-protein interaction (2005) Curr Protein Pept Sci, 6, pp. 151-169 Martin, E. J., Blaney, J. M., Siani, M. A., Spellmeyer, D. C., Wong, A. K., Moos, W. H., Measuring diversity: experimental design of combinatorial libraries for drug discovery (1995) J Med Chem, 38, pp. 1431-1436 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Geysen, H. M., Rodda, S. J., Mason, T. J., A priori delineation of a peptide which mimics a discontinuous antigenic determinant (1986) Mol Immunol, 23, pp. 709-715 Flier, J. S., Insulin receptors and insulin resistance (1983) Annu Rev Med, 34, pp. 145-160 Cheng, A. C., Coleman, R. G., Smyth, K. T., Cao, Q., Soulard, P., Caffrey, D. R., Salzberg, A. C., Huang, E. S., Structure-based maximal affinity model predicts small-molecule druggability (2007) Nat Biotechnol, 25, pp. 71-75 Arkin, M. R., Randal, M., DeLano, W. L., Hyde, J., Luong, T. N., Oslob, J. D., Raphael, D. R., Braisted, A. C., Binding of small molecules to an adaptive protein-protein interface (2003) Proc Natl Acad Sci USA, 100, pp. 1603-1608 Sidhu, S. S., Fairbrother, W. J., Deshayes, K., Exploring protein-protein interactions with phage display (2003) Chembiochem, 4, pp. 14-25 Pillutla, R. C., Hsiao, K. C., Beasley, J. R., Brandt, J., Ostergaard, S., Hansen, P. H., Spetzler, J. C., Goldstein, N. I., Peptides identify the critical hotspots involved in the biological activation of the insulin receptor (2002) J Biol Chem, 277, pp. 22590-22594 Nakamura, G. R., Reynolds, M. E., Chen, Y. M., Starovasnik, M. A., Lowman, H. B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc Natl Acad Sci USA, 99, pp. 1303-1308 Besterman, J. M., Duronio, V., Cuatrecasas, P., Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger (1986) Proc Natl Acad Sci USA, 83, pp. 6785-6789 Sung, T. C., Zhang, Y., Morris, A. J., Frohman, M. A., Structural analysis of human phospholipase D1 (1999) J Biol Chem, 274, pp. 3659-3666 Xie, Z., Ho, W. T., Exton, J., Association of the N- and C-terminal domains of Phospholipase D is required for catalytic activity (1998) J Biol Chem, 273, pp. 34679-34682}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Biological Sciences, School of Biotechnological Sciences, University of Naples Federico II, Via Mezzocannone, 16, 80134, Naples, Italy Department of Pharmaceutical and Toxicological Chemistry, University of Naples ''Federico II'', Via Montesano 49, Naples, Italy Institute of Biostructures and Bioimaging - CNR, Via Mezzocannone 16, 80134, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_50961, author={Ronga L, Langella E, Palladino P, Marasco D, Tizzano B, Saviano M, Pedone C, Improta R, Ruvo M}, title={Does Tetracycline Bind Helix 2 Of Prion? An Integrated Spectroscopical And Computational Study Of The Interaction Between The Antibiotic And Alpha Helix 2 Human Prion Protein Fragments}, date={2007 Feb 15}, journal={Proteins (ISSN: 0887-3585, 1097-0134, 1097-0134electronic)}, year={2007}, fullvolume={437}, volume={437}, pages={707--715}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33846202560&partnerID=40&md5=c035398b7f05be92579f3b9e038ab62a}, abstract={We demonstrate here that tetracycline (TC) can strongly interact (K-D = 189 +/- 7 nM) with model peptides derived from the C-terminal globular domain of the prion protein, hPrP [173-195], and that interaction concerns residues within the C-terminal half of the helix 2, a short region previously indicated as endowed with ambivalent conformational behavior and implicated in PrP conversion to the P-sheet-rich, infective scrapie variant. Data have been confirmed by binding studies with the N-terminal truncated 180-195 variant that displays a dissociation constant of 483 +/- 30 nM. Remarkably, TC does not influence the structure of the N-terminally fluoresceinated peptides that both show alpha-helical conformations. Docking calculations and molecular dynamics simulations suggest a direct, strong interaction of the antibiotic with exposed side chain functional groups of threonines 190-193 on the solvent-exposed surface of helix 2. Proteins 2007; 66: 707-715. (c) 2006 Wiley-Liss, Inc}, keywords={Cd Spectroscopy, Docking Calculations, Fluorescence Spectroscopy, Molecular Dynamics, Prion Peptides, Tetracycline, Antibiotic Agent, Prion Protein, Solvent, Threonine, Alpha Helix, Amino Terminal Sequence, Antibiotic Therapy, Beta Sheet, Carboxy Terminal Sequence, Conference Paper, Dissociation Constant, Drug Protein Binding, Human, Mathematical Computing, Priority Journal, Protein Conformation, Protein Interaction, Solvent Effect, Amino Acid Sequence, Anti-Bacterial Agents, Circular Dichroism, Kinetics, Molecular Sequence Data, Spectrometry, }, references={Porat, Y., Ambramotitz, A., Gazit, E., Inhibition of amyloid fibril formation by polyphenols: Structural similarity and aromatic interactions as a common inhibition mechanism (2006) Chem Biol Drug Des, 67, pp. 27-3 May, B.C.H., Fafarman, A.T., Hong, S.B., Rogers, M., Deady, L.W., Prusiner, S.B., Cohen, F.E., Potent inhibition of scrapie prion replication in cultured cells by bis-acridines (2003) Proc Natl Acad Sci USA, 100, pp. 3416-3421 Tagliavini, F., Forloni, G., Colombo, L., Rossi, G., Girala, L., Canciani, B., Angeretti, N., Salmona, M., Tetracycline affects abnormal properties of synthetic PrP peptides and PrPSc in vitro (2000) J Mol Biol, 300, pp. 1309-1322 Forloni, G., Iussich, S., Awan, T., Colombo, L., Angeretti, N., Girala, L., Bertani, I., Tagliavini, F., Tetracyclines affect prion infectivity (2002) Proc Natl Acad Sci USA, 99, pp. 10849-10854 Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O., Tagliavini, F., Neurotoxicity of a prion protein fragment (1993) Nature, 362, pp. 543-546 Forloni, G., Del Bo, R., Angeretti, N., Chiesa, R., Smiroldo, S., Doni, R., Ghigaudi, E., Tagliavini, F., A neurotoxic prion protein fragment induces rat astroglial proliferation and hypertrophy (1994) Eur J Neurosci, 6, pp. 1415-1422 Selvaggini, C., Del Gioia, L., Cantù, L., Ghibaudi, E., Diomede, L., Psserini, F., Forloni, G., Salmona, M., Molecular characteristics of a protease-resistant amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein (1993) Biochem Biophys Res, 194, pp. 1380-1386 Tagliavini, F., Prelli, F., Verga, L., Giaccone, G., Sarma, R., Gorevic, P., Ghetti, B., Frangione, B., Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro (1993) Proc Natl Acad Sci USA, 90, pp. 9678-9682 Brown, D., Schmidt, B., Kretzschmar, H.A., Role of microglia and host prion protein in neurotoxicity of a prion protein fragment (1996) Nature, 380, pp. 345-347 Knaus, K.J., Morillas, M., Swietnicki, W., Malone, M., Surewicz, W., Yee, V.C., Crystal structure of the human prion protein reveals a mechanism for oligomerization (2001) Nat Struct Biol, 8, pp. 770-774 Zahn, R., Liu, A., Lührs, T., Riek, R., von Schroetter, C., Garcia, F.L., Billeter, M., Wüthrich, K., NMR solution structure of the human prion protein (2000) Proc Natl Acad Sci USA, 97, pp. 145-150 Tizzano, B., Palladino, P., De Capua, A., Marasco, D., Rossi, F., Benedetti, E., Pedone, C., Ruvo, M., The human prion protein α2 helix: A thermodynamic study of its conformational preferences. 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M., Vasisht, N., Gill, A. C., Verma, C., Dodson, E. J., Dodson, G. G., Bayley, P. M., The crystal structure of the globular domain of sheep prion protein (2003) J Mol Biol, 336, pp. 1175-1183 Chou, P. Y., Fasman, G. D., Prediction of protein conformation (1974) Biochemistry, 13, pp. 222-245 Abramov, A. Y., Canevari, L., Duchen, M. R., Calcium signals induced by amyloid beta peptide and their consequences in neurons and astrocytes in culture (2004) Biochim Biophys Acta, 6, pp. 81-87 Othersen, O. G., Beierlein, F., Lanig, H., Clark, T., Conformations and tautomers of tetracycline (2003) J Phys Chem B, 107, pp. 13743-13749 Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., Olson, A. J., Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function (1998) J Comput Chem, 19, pp. 1639-1662 Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., Hermans, J., (1981) Intermolecular Forces, pp. 331-342. , Pullman, B, editor, Dordrecht, The Netherlands: Reidel 1986van Buuren, A. R. S., Marrink, J., Berendsen, H. J. C., A molecular dynamics study of the decane/water interface (1993) J Phys Chem, 97, pp. 9206-9212 D'Ursi, A. M., Arenante, M. R., Guerrini, R., Salvatori, S., Sorrentino, G., Picone, D., Solution structure of amyloid -peptide 25-35 in different media (2004) J Med Chem, 47, pp. 4231-4238 Dima, R. I., Thirumalai, D., Probing the instabilities in the dynamics of helical fragments from mouse PrPC (2004) Proc Natl Acad Sci USA, 101, pp. 15335-15340 Shamsir, M. S., Dalby, A. R., One gene two diseases and three conformations: Molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. Proteins: Struct Funct (2005) Bioinform, 59, pp. 72-79}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini del CNR, Sezione Biostrutture, via Mezzocannone 16, 80134 Napoli, Italy Dipartimento delle Scienze Biologiche, Sezione Biostrutture, Università Federico II, via Mezzocannone, 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_52926, author={Strizzi L, Sandomenico A, Margaryan NV, Foca A, Sanguigno L, Bodenstine TM, Chandler GS, Reed DW, Gilgur A, Seftor EA, Seftor RE, Khalkhali-ellis Z, Leonardi A, Ruvo M, Hendrix MJ}, title={Effects of a novel Nodal-targeting monoclonal antibody in melanoma}, date={2015 Oct 27}, journal={Oncotarget (ISSN: 1949-2553, 1949-2553electronic)}, year={2015}, fullvolume={207}, volume={207}, pages={34071--34086}, url={}, abstract={Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.}, keywords={Nodal, Cancer, Antibody, Elisa, Therapy, }, references={}, document_type={Journal Article, }, affiliation={1 Cancer Biology and Epigenomics Program, Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s 2 Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 3 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 4 Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 5 Istituto di Biostrutture e Bioimmagini del CNR and CIRPeB, Università Federico II di Napoli, Naples, Italy 6 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, Naples, Italy * These authors have contributed equally to this work}, ibbaffiliation={1}, } @article{IBB_ID_9159, author={Guarnieri D, Borzacchiello A, De Capua A, Ruvo M, Netti P}, title={Engineering of covalently immobilized gradients of RGD peptides on hydrogel scaffolds: Effect on cell behaviour}, date={2008}, journal={Macromol Sympos (ISSN: 1022-1360)}, year={2008}, fullvolume={394}, volume={394}, pages={36--40}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-54949119915&partnerID=40&md5=5ded8d1645e9122ec0fcc71679c04b7d}, abstract={The aim of this study has been to design a system for the preparation of Polyethylene-glycol (PEG) based hydrogels with a controlled spatial distribution of covalently immobilised RGD adhesion signals in order to control and guide cell response for tissue engineering application. Gradients of immobilised RGD peptides were characterized by confocal microscopy analysis. Moreover, the effect of RGD spatial distribution on cell behaviour was evaluated by using mouse embryo fibroblasts NIH3T3. In particular, we observed cell adhesion and migration of fibroblasts seeded on RGD gradient compared to cells on control hydrogels having an uniform distribution of RGD. Our data suggest that a linear gradient of covalently immobilised adhesion signals affects cell behaviour. In particular, cells feel RGD gradient and oriented themselves and move along gradient direction. Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA.}, keywords={Gradient, Hydrogel, Polyethylene-Glycol, Scaffold, Adhesion, Amines, Cell Adhesion, Cell Culture, Colloids, Confocal Microscopy, Cytology, Ethylene Glycol, Fibroblasts, Microscopic Examination, Peptides, Polyethylene Glycols, Polyethylene Oxides, Proteins, Size Distribution, Thermoplastics, Tissue Engineering, Adhesion Signals, Cell Behaviours, Cell Responses, Covalently Immobilized, Gradient Directions, Hydrogel Scaffolds, Linear Gradients, Mouse Embryo Fibroblasts, Rgd Peptides, Spatial Distribution Of, Tissue Engineering Applications, Uniform Distributions, }, references={Martin, P., (1997) Science, 276, pp. 75-8 Gobin, A.S., West, J.L., FASEB, 1002 (7), pp. 751-753. , J16 Friedl, P., Borgmann, S., Bröcker, E.B., (2001) J Leukoc Biol, 70 (4), pp. 491-509 Griffith, L.G., (2002) Ann NY Acad Sci, 961, pp. 83-95 Maheshwari, G., Brown, G., Lauffenburger, D.A., Wells, A., Griffith, L.G., (2000) Cell Sci, 113 (PART 10), pp. 1677-1686 Hubbell, J.A., (1999) Tissue Engineering of vascular prosthetic grafts, pp. 561-570. , RG Landes Company, Austin Hern, D.L., Hubbell, J.A., (1998) J. Biomed. Mater. Res, 39, pp. 266-276 Burdick, J.A., Anseth, K.S., (2002) Biomaterials, 23, pp. 4315-4323 Mann, B.K., Gobin, A.S., Tsal, A.T., Schmedlen, R.H., West, J.L., (2001) Biomaterials, 22, pp. 3045-3051 Stokes, C.L., Lauffenburger, D.A., (1991) J Theor Biol, 152 (3), pp. 377-403 Gobin, A. S., West, J. L., FASEB, 1002 (7), pp. 751-753. , J16 Griffith, L. G., (2002) Ann NY Acad Sci, 961, pp. 83-95 Hubbell, J. A., (1999) Tissue Engineering of vascular prosthetic grafts, pp. 561-570. , RG Landes Company, Austin Hern, D. L., Hubbell, J. A., (1998) J. Biomed. Mater. Res, 39, pp. 266-276 Burdick, J. A., Anseth, K. S., (2002) Biomaterials, 23, pp. 4315-4323 Mann, B. K., Gobin, A. S., Tsal, A. T., Schmedlen, R. H., West, J. L., (2001) Biomaterials, 22, pp. 3045-3051 Stokes, C. L., Lauffenburger, D. A., (1991) J Theor Biol, 152 (3), pp. 377-403}, document_type={Journal Article, }, affiliation={Interdisciplinary Centre of Biomedical Materials (CRIB), University of Naples Federico II, P.le Tecchio 80, 80125 Naples, Italy Institute of Composite and Biomedical Materials, National Research Council, P.le Tecchio 80, 80125 Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone, 16, 80134 - Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_50836, author={Verdoliva A, Marasco D, De Capua A, Saporito A, Bellofiore P, Manfredi V, Fattorusso R, Pedone C, Ruvo M}, title={Erratum: A new ligand for immunoglobulin G subdomains by screening of a synthetic peptide library (ChemBioChem (2005) 6 (1242-1253))}, date={2005}, journal={Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-7633electronic)}, year={2005}, fullvolume={237}, volume={237}, pages={1307--1307}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-23644435317&partnerID=40&md5=d3812c3d5aee5fd0260139e18185ba8e}, abstract={}, keywords={Erratum, Priority Journal, }, references={}, document_type={Erratum, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_53483, author={Caporale A, Doti N, Sandomenico A, Ruvo M}, title={Evaluation of combined use of Oxyma and HATU in aggregating peptide sequences}, date={2017 Apr}, journal={J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617linking)}, year={2017}, fullvolume={401}, volume={401}, pages={272--281}, url={}, abstract={Polypeptides are finding increasing applications as therapeutics because of their specificity that often translates into excellent safety, tolerability, and efficacy profiles in humans. New synthetic methodologies for their preparation are thereby continuously sought to reduce the costs associated to chain assembly and purification. Although solid-phase peptide synthesis has become one of the most advanced synthetic procedures at both laboratory and industrial scale, the process is often complicated by aggregation phenomena originating from the combined occurrence of intermolecular and intramolecular hydrogen bonding, hydrophobic interactions, or other effects. Altogether, these effects cause accumulation of many side products and synthetic mixtures extremely hard to separate and purify, strongly affecting the costs of the final material. In the attempt to optimize the coupling steps of some well-known aggregating or otherwise difficult to obtain peptides, we have comparatively investigated the use of Oxyma/DIC and HATU/Sym-collidine as second coupling reagents in double coupling settings for the preparation of some model peptides. Comparative analytical data obtained on the unpurified products with the two different protocols clearly show that the use of Oxyma/DIC largely improves the content of the target molecules in the final crude materials, making the synthesis more convenient and cost-effective. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.}, keywords={Amino Acid Sequence, Aza Compounds, Chemistry, Humans, Peptides, Chemical Synthesis, Pregnadienes, Solid-Phase Synthesis Techniques, Triazoles, Difficult Peptide Sequences, Oxyma, Solid Phase Peptide Synthesis (spps), }, references={}, document_type={Journal Article, }, affiliation={IBB-CNR and CIRPeB, Via Mezzocannone 16, 80134, Naples, Italy., }, ibbaffiliation={1}, } @article{IBB_ID_54444, author={Sandomenico A, Sivaccumar JP, Ruvo M}, title={Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments}, date={2020 Aug 31}, journal={Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596)}, year={2020}, fullvolume={49}, volume={49}, pages={N/D--N/D}, url={}, abstract={Antibodies and antibody-derived molecules are continuously developed as both therapeutic agents and key reagents for advanced diagnostic investigations. Their application in these fields has indeed greatly expanded the demand of these molecules and the need for their production in high yield and purity. While full-length antibodies require mammalian expression systems due to the occurrence of functionally and structurally important glycosylations, most antibody fragments and antibody-like molecules are non-glycosylated and can be more conveniently prepared in E. coli-based expression platforms. We propose here an updated survey of the most effective and appropriate methods of preparation of antibody fragments that exploit E. coli as an expression background and review the pros and cons of the different platforms available today. Around 250 references accompany and complete the review together with some lists of the most important new antibody-like molecules that are on the market or are being developed as new biotherapeutics or diagnostic agents.}, keywords={E Coli, Fab, Antibody Fragment, Scfv, }, references={}, document_type={Journal Article, Review, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone, 16, 80134 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54559, author={Chelko SP, Keceli G, Carpi A, Doti N, Agrimi J, Asimaki A, Beti CB, Miyamoto M, Amat-codina N, Bedja D, Wei AC, Murray B, Tichnell C, Kwon C, Calkins H, James CA, O, #rourke B, Halushka MK, Melloni E, Saffitz JE, Judge DP, Ruvo M, Kitsis RN, Andersen P, Di Lisa F, Paolocci N}, title={Exercise triggers CAPN1-mediated AIF truncation, inducing myocyte cell death in arrhythmogenic cardiomyopathy}, date={2021 Feb 17}, journal={Sci Transl Med (ISSN: 1946-6234linking)}, year={2021}, fullvolume={128}, volume={128}, pages={N/D--N/D}, url={https://stm.sciencemag.org/content/13/581/eabf0891}, abstract={Myocyte death occurs in many inherited and acquired cardiomyopathies, including arrhythmogenic cardiomyopathy (ACM), a genetic heart disease plagued by the prevalence of sudden cardiac death. Individuals with ACM and harboring pathogenic desmosomal variants, such as desmoglein-2 (DSG2), often show myocyte necrosis with progression to exercise-associated heart failure. Here, we showed that homozygous Dsg2 mutant mice (Dsg2 (mut/mut)), a model of ACM, die prematurely during swimming and display myocardial dysfunction and necrosis. We detected calcium (Ca(2+)) overload in Dsg2 (mut/mut) hearts, which induced calpain-1 (CAPN1) activation, association of CAPN1 with mitochondria, and CAPN1-induced cleavage of mitochondrial-bound apoptosis-inducing factor (AIF). Cleaved AIF translocated to the myocyte nucleus triggering large-scale DNA fragmentation and cell death, an effect potentiated by mitochondrial-driven AIF oxidation. Posttranslational oxidation of AIF cysteine residues was due, in part, to a depleted mitochondrial thioredoxin-2 redox system. Hearts from exercised Dsg2 (mut/mut) mice were depleted of calpastatin (CAST), an endogenous CAPN1 inhibitor, and overexpressing CAST in myocytes protected against Ca(2+) overload-induced necrosis. When cardiomyocytes differentiated from Dsg2 (mut/mut) embryonic stem cells (ES-CMs) were challenged with β-adrenergic stimulation, CAPN1 inhibition attenuated CAPN1-induced AIF truncation. In addition, pretreatment of Dsg2 (mut/mut) ES-CMs with an AIF-mimetic peptide, mirroring the cyclophilin-A (PPIA) binding site of AIF, blocked PPIA-mediated AIF-nuclear translocation, and reduced both apoptosis and necrosis. Thus, preventing CAPN1-induced AIF-truncation or barring binding of AIF to the nuclear chaperone, PPIA, may avert myocyte death and, ultimately, disease progression to heart failure in ACM and likely other forms of cardiomyopathies.}, keywords={Animals, Apoptosis Inducing Factor Metabolism, Calpain Metabolism, Cardiomyopathies Metabolism, Cell Death, Mice, Mitochondria Metabolism, Myocytes, Cardiac Metabolism Pathology, Physical Conditioning}, references={}, document_type={Journal Article, Research Support, N. I. H. , Extramural, Non-U. S. Gov'T}, affiliation={Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA. stephen.chelko@med.fsu.edu npaoloc1@jhmi.edu., Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Department of Biomedical Sciences, University of Padova, Padova 35122, Italy., Institute of Biostructures and Bioimaging, CNR, Naples 80134, Italy., Molecular and Clinical Sciences Research Institute, St. George's, University of London, London WC1E 6BS, UK., Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia., Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Department of Medicine, University of Genova, Genova 16126, Italy., Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 20115, USA., Medical University of South Carolina, Charleston, SC 29425, USA., Departments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. stephen.chelko@med.fsu.edu npaoloc1@jhmi.edu., }, ibbaffiliation={1}, } @article{IBB_ID_54453, author={Valletta M, Russo R, Baglivo I, Russo V, Ragucci S, Sandomenico A, Iaccarino E, Ruvo M, De Feis I, Angelini C, Iachettini S, Biroccio A, Pedone PV, Chambery A}, title={Exploring the Interaction between the SWI/SNF Chromatin Remodeling Complex and the Zinc Finger Factor CTCF}, date={2020 Nov 25}, journal={Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596)}, year={2020}, fullvolume={56}, volume={56}, pages={N/D--N/D}, url={}, abstract={The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships among many CTCF-mediated activities involves direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases, and BRG1, further supports the interplay between master regulators of mammalian genome folding. Here, we report a comprehensive LC-MS/MS mapping of the components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature, and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4-8 of CTCF, thus, suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.}, keywords={Brg1, Ctcf, Swi Snf, Chromatin, Mass Spectrometry, Protein–protein Interaction, Transcription Factor, }, references={}, document_type={Journal Article, }, affiliation={Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy. Istituto di Biostrutture e Bioimmagini IBB, National Research Council, 80134 Napoli, Italy. Istituto per le Applicazioni del Calcolo IAC 'M. Picone', National Research Council, 80131 Napoli, Italy. Oncogenomic and Epigenetic Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Roma, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_48762, author={Viparelli F, Doti N, Sandomenico A, Marasco D, Dathan NA, Miele C, Beguinot F, Monti SM, Ruvo M}, title={Expression and purification of the D4 region of PLD1 and characterization of its interaction with PED-PEA15}, date={2008 Jun}, journal={Protein Expr Purif (ISSN: 1046-5928)}, year={2008}, fullvolume={419}, volume={419}, pages={302--308}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-42749089546&partnerID=40&md5=17dd299046dc8eb5c67b73e880bcba43}, abstract={PLD's (Phospholipases D) are ubiquitously expressed proteins involved in many transphosphatidylation reactions. They have a bi-lobed structure composed by two similar domains which at their interface reconstitute the catalytic site through the association of the two conserved HxKx4Dx6GSxN motifs. PLD1 interacts with the small phosphoprotein PED-PEA15 by an unknown mechanism that, by enhancing PLD1 stability, apparently increases its enzymatic activity; the minimum interacting region of PLD1 was previously identified as spanning residues 712-1074 (D4 region). Since the D4/PED-PEA15 interaction has been claimed to be one of the multiple molecular events that can trigger type 2 diabetes, we purified the two recombinant proteins to study in vitro this binding by both ELISA and SPR techniques. Whilst PED-PEA15 was easily expressed and purified, expression of recombinant D4 was more problematic and only the fusion protein with Thioredoxin A and a six Histidine Tag (Trx-His6-D4) demonstrated sufficient stability for further characterization. We have found that Trx-His6-D4 is present as two different oligomeric forms, though only the monomeric variant is able to interact with PED-PEA15. All these findings may have important implications for both the mechanisms of phospholipase activity and PED-PEA15 regulative functions. © 2008 Elsevier Inc. All rights reserved.}, keywords={Phospholipase, Phosphoprotein Enriched In Diabetes (ped), Protein-Protein Interaction, Pea15 Protein, Human, Phospholipase D1, Signal Peptide, Article, Biosynthesis, Chemistry, Enzyme Linked Immunosorbent Assay, Genetics, Isolation And Purification, Molecular Cloning, Protein Tertiary Structure, Surface Plasmon Resonance, Enzyme-Linked Immunosorbent Assay, Intracellular Signaling Peptides And Proteins, Protein Structure, }, references={McDermott, M., Wakelam, M.J.O., Morris, A.J., Phospholipase D 1,2, Biochem (2004) Cell Biol., 82, pp. 225-25 Besterman, J.M., Duronio, V., Cuatrecasa, P., Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger (1986) Proc. Natl. Acad. Sci. USA, 83, pp. 6785-6789 Sung, T.C., Zhang, Y., Morris, A.J., Frohman, M.A., Structural analysis of human phospholipase D1 (1999) J. Biol. Chem., 274, pp. 3659-3666 Sung, T.C., Altshuller, Y.M., Morris, A.J., Frohman, M.A., Molecular analysis of mammalian phospholipase D2 (1999) J. Biol. Chem., 274, pp. 494-502 Sung, T.C., Roper, R., Zhang, Y., Rudge, S.A., Temel, R., Hammond, S.M., Morris, A.J., Frohman, M.A., Mutagenesis of Phospholipase D defines a superfamily including a trans-golgi viral protein required for poxvirus pathogenicity (1997) EMBO J., 16, pp. 4519-4539 Stuckey, J.A., Dixon, J.E., Crystal structure of a phospholipase D member (1999) Nat. Struct. Biol., 6, pp. 278-284 Davies, D.R., Interthal, H., Champoux, J.J., Hol, W.G., The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1 (2002) Structure, 10, pp. 237-248 Leiros, I., Secundo, F., Zambonelli, C., Servi, S., Hough, E., The first crystal structure of a phospholipase D (2000) Structure, 8, pp. 655-667 Ponting, C.P., Kerr, I.D., A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues (1996) Protein Sci., 5, pp. 914-922 Xie, Z., Ho, W.T., Exton, J., Association of the N- and C-terminal domains of Phospholipase D (2000) J. Biol. Chem., 275, pp. 24962-24969 Kam, Y., Exton, J.H., Dimerization of phospholipase D isozymes (2002) Biochem. Biophys. Res. Commun., 290, pp. 375-380 Exton, J.H., Phospholipase D-structure, regulation and function (2002) Rev. Physiol. Biochem. Pharmacol., 144, pp. 1-94 Zhang, Y., Redina, O., Altshuller, Y.M., Yamazaki, M., Ramos, J., Chneiweiss, H., Kanaho, Y., Frohman, M.A., Regulation of expression of Phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them (2000) J. Biol. Chem., 275, pp. 35224-35232 Vigliotta, G., Miele, C., Santopietro, S., Portella, G., Perfetti, A., Maitan, M.A., Cassese, A., Beguinot, F., Overexpression of the PED/PEA15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action (2004) Mol. Cell. Biol., 24, pp. 5005-5015 Condorelli, G., Vigliotta, G., Iavarone, C., Caruso, M., Tocchetti, C.G., Andreozzi, F., Cafieri, A., Beguinot, F., PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus (1998) EMBO J., 17, pp. 3858-3866 Xiao, C., Yang, B.F., Asadi, N., Beguinot, F., Hao, C., Tumor necrosis factor-related apoptosis-inducing signaling complex and its modulation by c-Flip and PED/PEA-15 in glioma cells (2002) J. Biol. Chem., 277 (28), pp. 25020-25025 Condorelli, G., Trencia, A., Vigliotta, G., Perfetti, A., Goglia, U., Cassese, A., Musti, A.M., Beguinot, F., Multiple members of the mitogen-activated protein kinase family are necessary for PED/PEA15 anti-apoptotic function (2002) J. Biol. Chem., 277, pp. 11013-11018 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxylmethyl dextran modified gold surface for biospecific interaction analysis in SPR sensors (1991) Anal. Biochem., 198, pp. 268-277 Hill, J.M., Vaidyanathan, H., Ramos, J.W., Ginsberg, M.H., Werner, M.H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) EMBO J., 21, pp. 6494-6504}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134 Napoli, Italy Dipartimento di Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone, 16, 80134 Napoli, Italy Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Via S.M. di Costantinopoli 16, 80138 Napoli, Italy Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS), CNR, Via Pansini, 5, 80131 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53649, author={Aliberti A, Vaiano P, Caporale A, Consales M, Ruvo M, Cusano A}, title={Fluorescent chemosensors for Hg2+ detection in aqueous environment}, date={2017 Aug}, journal={Sensors And Actuators}, year={2017}, fullvolume={258}, volume={258}, pages={727--735}, url={https://doi.org/10.1016/j.snb.2017.03.026}, abstract={Mercury is a pollutant extremely toxic to the environment and human health. Although numerous methods have been reported for the analysis of Hg 2+ ions in water, the development of simple, rapid, inexpensive, and sensitive sensors still represents a challenge. Here, we describe the design, synthesis and spectral characterization of a set of dansyl-amino acids able to recognize Hg 2+ ions via different fluorescence emission modes. The analysis of the binding features of the different chemosensors shows that the stoichiometry of the sensor–Hg 2+ complex depends on the concentration of the sensor and Hg 2+ since it plays an important role in the type of response for Hg 2+ ions. Among those studied here N-dansylated methionine is the best performing chemosensor in terms of sensitivity with a LOD of 140 nM. To improve the LOD of this chemosensor, we evaluated the response of a portable experimental set-up based on optical fiber probes. The new device shows an increase of LOD from 140 nM to about 5 nM, which can meet the requirements imposed by the Environmental Protection Agency for monitoring Hg 2+ in drinkable water. We also show that the chemosensors are not applicable to marine water-based matrices because of the significant coordinating ability of chloride anions with Hg 2+ . Graphical abstract }, keywords={Mercury Ions, Fluorescence, Dansyl-Aminoacid, Optical Fiber Probe, }, references={}, document_type={Journal Article, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, I-82100 Benevento, Italy Institute of Biostructure and Bioimaging, National Research Council, I-80143 Naples, Italy Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University “Federico II”, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53485, author={Caporale A, Mascanzoni F, Farina B, Sturlese M, Di Sorbo G, Fattorusso R, Ruvo M, Doti N}, title={FRET-Protease-Coupled Peptidyl-Prolyl cis-trans Isomerase Assay: New Internally Quenched Fluorogenic Substrates for High-Throughput Screening}, date={2016 Aug}, journal={J Biomol Screen (ISSN: 1087-0571, 1552-454x)}, year={2016}, fullvolume={247}, volume={247}, pages={701--712}, url={}, abstract={In this work, a sensitive and convenient protease-based fluorimetric high-throughput screening (HTS) assay for determining peptidyl-prolyl cis-trans isomerase activity was developed. The assay was based on a new intramolecularly quenched substrate, whose fluorescence and structural properties were examined together with kinetic constants and the effects of solvents on its isomerization process. Pilot screens performed using the Library of Pharmacologically Active Compounds (LOPAC) and cyclophilin A (CypA), as isomerase model enzyme, indicated that the assay was robust for HTS, and that comparable results were obtained with a CypA inhibitor tested both manually and automatically. Moreover, a new compound that inhibits CypA activity with an IC50 in the low micromolar range was identified. Molecular docking studies revealed that the molecule shows a notable shape complementarity with the catalytic pocket confirming the experimental observations. Due to its simplicity and precision in the determination of extent of inhibition and reaction rates required for kinetic analysis, this assay offers many advantages over other commonly used assays.}, keywords={Edans-Dabcyl Pairs, Hts, Chymotrypsin-Coupled Assay, Fluorescence, Prolyl-Peptidyl Isomerases, }, references={}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini-CNR and CIRPEB, Napoli, Italy Dipartimento di Farmacia, Universita di Napoli "Federico II", Napoli, Italy., Istituto di Biostrutture e Bioimmagini-CNR and CIRPEB, Napoli, Italy., Molecular Modeling Section, Dipartimento di Scienze del Farmaco, Universita di Padova, Padova, Italy., Istituto di Biostrutture e Bioimmagini-CNR and CIRPEB, Napoli, Italy Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy., Istituto di Biostrutture e Bioimmagini-CNR and CIRPEB, Napoli, Italy nunzianna.doti@cnr.it., }, ibbaffiliation={1}, } @article{IBB_ID_52565, author={Tornatore L, Marasco D, Dathan N, Vitale RM, Benedetti E, Papa S, Franzoso G, Ruvo M, Monti SM}, title={Gadd45 beta forms a homodimeric complex that binds tightly to MKK7}, date={2008 Apr 18}, journal={J Mol Biol (ISSN: 0022-2836, 0022-2283, 1089-8638)}, year={2008}, fullvolume={427}, volume={427}, pages={97--111}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-41149088639&partnerID=40&md5=f36e591f01a141b3380f20e278f80458}, abstract={Gadd45 alpha, beta, and gamma proteins, also known as growth arrest and DNA damage-inducible factors, have a number of cellular functions, including cell-cycle regulation and propagation of signals produced by a variety of cellular stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45 beta has been indicated as a major player in the endogenous NF-kappa B-mediated resistance to apoptosis in a variety of cell lines. In fibroblasts this mechanism involves the inactivation of MKK7, the upstream activator of JNK, by direct binding within the kinase ATP pocket. On the basis of a number of experimental data, the structures of Gadd45 beta and the Gadd45 beta-MKK7 complex have been predicted recently and data show that interactions are mediated by acidic loops 1 and 2, and helices 3 and 4 of Gadd45 beta. Here, we provide further evidence that Gadd45 beta is a prevailingly alpha-helical protein and that in solution it is able to form non covalent dimers but not higher-order oligomers, in contrast to what has been reported for the homologous Gadd45 alpha. We show that the contact region between the two monomers is comprised of the predicted helix 1 (residues Q17-Q33) and helix 5 (residues K131-R146) of the protein, which appear to be antiparallel and to form a large dimerisation surface not involved in MKK7 recognition. The results suggest the occurrence of a large complex containing at least an MKK7-Gadd45 beta: Gadd45 beta -MKK7 tetrameric unit whose complexity could be further increased by the dimeric nature of the isolated MKK7}, keywords={Dimerization, Gadd45b, Mkk7, Oligomerization, Protein-Protein Interaction, Growth Arrest And Dna Damage Inducible Protein 45, Mitogen Activated Protein Kinase Kinase 7, Article, Biotinylation, Circular Dichroism, Enzyme Isolation, Gel Electrophoresis, Peptide Synthesis, Priority Journal, Protein Binding, Protein Expression, Protein Purification, Amino Acid Sequence, Antigens, Differentiation, Chromatography, Humans, Map Kinase Kinase 7, Molecular Sequence Data, Protein Conformation, Protein Interaction Mapping, Chemistry, Genetics, }, references={Papa, S., Monti, S. M., Vitale, R. M., Bubici, C., Jayawardena, S., Alvarez, K., Insights into the structural basis of the GADD45beta -mediated inactivation of the JNK kinase, MKK7/JNKK2 (2007) J. Biol. 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A., Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control (2000) J. Biol. Chem., 275, pp. 16810-16819 Smith, M. L., Chen, I. T., Zhan, Q., Bae, I., Chen, C. Y., Gilmer, T. M., Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen (1994) Science, 266, pp. 1376-1380 Wang, X. W., Zhan, Q., Coursen, J. D., Khan, M. A., Kontny, H. U., Yu, L., GADD45 induction of a G2/M cell cycle checkpoint (1999) Proc. Natl Acad. Sci. 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C., Yagita, H., An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway (2006) EMBO J., 25, pp. 5549-5559 Cobb, M. H., Goldsmith, E. J., Dimerization in MAP-kinase signaling (2000) Trends Biochem. Sci., 25, pp. 7-9 Pelech, S., Dimerization in protein kinase signaling (2006) J. Biol., 5, p. 12 Carrier, F., Georgel, P. T., Pourquier, P., Blake, M., Kontny, H. U., Antinore, M. J., Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin (1999) Mol. Cell Biol., 19, pp. 1673-1685 (1999) Current Protocols in Protein Science, 2, pp. 10. 3. 5-10. 3. 10. , Coligan J. E., Dunn B. M., Speicher D. W., and Wingfild P. T. (Eds), John Wiley & sons Inc., Hobochen, NJ Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Scalable molecular dynamics with NAMD (2005) J. Comput. Chem., 26, pp. 1781-1802 MacKerell, A. D., Bashford, D., Bellott, M., Dunbrack, R. L., Evanseck, J. D., Field, M. J., All-atom empirical potential for molecular modeling and dynamics studies of proteins (1998) J. Phys. Chem., 102, pp. 3586-3616 Koradi, R., Billeter, M., Wuthrich, K., MOLMOL: a program for display and analysis of macromolecular structures (1996) J. Mol. Graph., 14, pp. 51-55}, document_type={Abstract, Conference, Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134 Napoli, Italy Dipartimento delle Scienze Biologiche, via Mezzocannone, 16, 80134 Napoli, Italy Istituto di Chimica Biomolecolare (ICB), CNR, Via Campi Flegrei, 34, 80078 Pozzuoli, NA, Italy Department of Immunology at Hammersmith, Division of Investigative Science, Imperial College, London, Du Cane Road, London, W12 ONN, United Kingdom}, ibbaffiliation={1}, } @article{IBB_ID_52261, author={Tornatore L, Montil SM, Marasco D, Dathan N, Vitale RM, Benedetti E, Pedone C, Papa S, Franzoso G, Ruvo M}, title={Gadd45beta dimerization does not affect MKK7 binding}, date={2009}, journal={Adv Exp Med Biol (ISSN: 0065-2598, 0065-2598print)}, year={2009}, fullvolume={333}, volume={333}, pages={367--368}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-66349083912&partnerID=40&md5=e080aae67d81a0f3c815cec4b918ab2e}, abstract={}, keywords={Differentiation Antigen, Mitogen Activated Protein Kinase Kinase 7, Article, Chemical Structure, Chemistry, Dimerization, Enzyme Active Site, Metabolism, Catalytic Domain, Map Kinase Kinase 7, Models, Molecular, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini - CNR, via Mezzocannone, 16, Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53117, author={Sandomenico A, Leonardi A, Berisio R, Sanguigno L, Foca G, Foca A, Ruggiero A, Doti N, Muscariello L, Barone D, Farina C, Owsianka A, Vitagliano L, Patel AH, Ruvo M}, title={Generation and characterization of monoclonal antibodies against a cyclic variant of Hepatitis C Virus E2 epitope 412-422}, date={2016 Jan 27}, journal={J Virol (ISSN: 0022-538x, 0022-538xlinking)}, year={2016}, fullvolume={192}, volume={192}, pages={3745--3759}, url={https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84960970619&partnerID=40&md5=3d81594004333ceaab06bfa63de086d6}, abstract={The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for virus entry into hepatocytes. A conserved region of E2 encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical for virus entry, is recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt a β-hairpin conformation when bound to neutralizing monoclonal antibodies (MAbs) AP33 and HCV1. We therefore generated new mouse MAbs that were able to bind to a cyclic peptide containing E2 residues 412 to 422 (C-epitope I) but not to the linear counterpart. These MAbs bound to purified E2 with affinities of about 50 nM, but they were unable to neutralize virus infection. Structural analysis of the complex between C-epitope I and one of our MAbs (C2) showed that the Trp420 side chain is largely buried in the combining site and that the Asn417 side chain, which is glycosylated in E2 and solvent exposed in other complexes, is slightly buried upon C2 binding. Also, the orientation of the cyclic peptide in the antibody-combining site is rotated by 180° compared to the orientations of the other complexes. All these structural features, however, do not explain the lack of neutralization activity. This is instead ascribed to the high degree of selectivity of the new MAbs for the cyclic epitope and to their inability to interact with the epitope in more flexible and extended conformations, which recent data suggest play a role in the mechanisms of neutralization escape. IMPORTANCE: Hepatitis C virus (HCV) remains a major health care burden, affecting almost 3% of the global population. The conserved epitope comprising residues 412 to 423 of the viral E2 glycoprotein is a valid vaccine candidate because antibodies recognizing this region exhibit potent neutralizing activity. This epitope adopts a β-hairpin conformation when bound to neutralizing MAbs. We explored the potential of cyclic peptides mimicking this structure to elicit anti-HCV antibodies. MAbs that specifically recognize a cyclic variant of the epitope bind to soluble E2 with a lower affinity than other blocking antibodies and do not neutralize virus. The structure of the complex between one such MAb and the cyclic epitope, together with new structural data showing the linear peptide bound to neutralizing MAbs in extended conformations, suggests that the epitope displays a conformational flexibility that contributes to neutralization escape. Such features can be of major importance for the design of epitope-based anti-HCV vaccines.}, keywords={Animals , Antibodies, Monoclonal Chemistry Immunology Isolation, Purification , Epitopes, B-Lymphocyte Immunology , Hepacivirus Immunology , Hepatitis C Antibodies Chemistry Immunology Isolation, Inbred Balb C , Models, Molecular , Neutralization Tests , Protein Binding , Protein Conformation , Viral Envelope Proteins Chemistry Immunology, }, references={Mohd Hanafiah, K., Groeger, J., Flaxman, A.D., Wiersma, S.T., Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence (2013) Hepatology, 57, pp. 1333-1342. , http://dx.doi.org/10.1002/hep.2614 Galossi, A., Guarisco, R., Bellis, L., Puoti, C., Extrahepatic manifestations of chronic HCV infection (2007) J Gastrointestin Liver Dis, 16, pp. 65-73 Simmonds, P., Bukh, J., Combet, C., Deléage, G., Enomoto, N., Feinstone, S., Halfon, P., Widell, A., Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes (2005) Hepatology, 42, pp. 962-973. , http://dx.doi.org/10.1002/hep.20819 Smith, D.B., Bukh, J., Kuiken, C., Muerhoff, A.S., Rice, C.M., Stapleton, J.T., Simmonds, P., Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource (2014) Hepatology, 59, pp. 318-327. , http://dx.doi.org/10.1002/hep.26744 Belousova, V., Abd-Rabou, A.A., Mousa, S.A., Recent advances and future directions in the management of hepatitis C infections (2015) Pharmacol Ther, 145, pp. 92-102. , http://dx.doi.org/10.1016/j.pharmthera.2014.09.002 Lawitz, E., Sulkowski, M.S., Ghalib, R., Rodriguez-Torres, M., Younossi, Z.Y., Corregidor, A., DeJesus, E., Jacobson, I.M., Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in nonresponders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study (2014) Lancet, 384, pp. 1756-1765. , http://dx.doi.org/10.1016/S0140-6736(14)61036-9 Koretz, R.L., ACP journal club: review: telaprevir, boceprevir, simeprevir, or sofosbuvir improves response in HCV type 1 (2014) Ann Intern Med, 161, p. 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S. Gov'T, }, affiliation={Institute of Biostructures and Bioimaging, CNR and CIRPeB, University of Naples Federico II, Napoli, Italy., Dept. of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Napoli, Italy., Institute of Biostructures and Bioimaging, CNR and CIRPeB, University of Naples Federico II, Napoli, Italy Dept. of Pharmacy, University of Naples Federico II, Napoli, Italy., Kedrion SpA, Lucca, Italy., Institute of Biostructures and Bioimaging, CNR and CIRPeB, University of Naples Federico II, Napoli, Italy Second University of Naples., Medical Research Council - University of Glasgow Centre for Virus Research, Glasgow, UK., Medical Research Council - University of Glasgow Centre for Virus Research, Glasgow, UK. menotti.ruvo@unina.it arvind.patel@glasgow.ac.uk., Institute of Biostructures and Bioimaging, CNR and CIRPeB, University of Naples Federico II, Napoli, Italy menotti.ruvo@unina.it arvind.patel@glasgow.ac.uk., Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy Department of Pharmacy, University of Naples Federico II, Naples, Italy Bioker Multimedica, Naples, Italy Kedrion SpA, Lucca, Italy. Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.}, ibbaffiliation={1}, } @article{IBB_ID_49255, author={Marasco D, Stilo R, Sandomenico A, Monti SM, Tizzano B, De Capua A, Varricchio E, Liguoro D, Zotti T, Formisano S, Ruvo M, Vito P}, title={Generation And Functional Characterization Of A Bcl10-Inhibitory Peptide That Represses Nf-Kappa B Activation}, date={2009 Sep 15}, journal={Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking)}, year={2009}, fullvolume={375}, volume={375}, pages={553--561}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70249094317&partnerID=40&md5=87926be1bec7103dcecce36cbc1e7a85}, abstract={The molecular complex containing BCL10 and CARMA [CARD (caspase recruitment domain)-containing MAGUK (membrane-associated guanylate kinase)] proteins has recently been identified as a key component in the signal transduction pathways that regulate activation of the transcription factor NF-κB (nuclear factor κB) in lymphoid and non-lymphoid cells. Assembly of complexes containing BCL10 and CARMA proteins relies on homophilic interactions established between the CARDs of these proteins. In order to identify BCL10-inhibitory peptides, we have established a method of assaying peptides derived from the CARD of BCL10 in binding competition assays of CARD-CARD self-association. By this procedure, a short peptide corresponding to amino acid residues 91-98 of BCL10 has been selected as an effective inhibitor of protein self-association. When tested in cell assays for its capacity to block NF-κB activation, this peptide represses activation of NF-κB mediated by BCL10, CARMA3 and PMA/ionomycin stimulation. Collectively, these results indicate that residues 91-98 of BCL10 are involved in BCL10 self-association and also participate in the interaction with external partners. We also show that blocking of the CARD of BCL10 may potentially be used for the treatment of pathological conditions associated with inappropriate NF-ΚB activation. © The Authors Journal compilation. © 2009 Biochemical Society.}, keywords={Bcl10-Inhibitory Peptide, Caspase Recruitment Domain (card), Caspase Recruitment Domain-Containing Membrane-Associated Guanylate Kinase (carma), Nuclear Factor κb (nf-κb), Amino Acid Residues, Functional Characterization, In-Cell, Key Component, Lymphoid Cells, Molecular Complexes, Pathological Conditions, Self-Associations, Signal Transduction Pathways, Cell Membranes, Employment, Organic Acids, Transcription Factors, Association Reactions, Caspase Recruitment Domain Signaling Protein, Immunoglobulin Enhancer Binding Protein, Membrane Associated Guanylate Cyclase Kinase, Protein Bcl 10, Bcl10 Protein, Human, Signal Transducing Adaptor Protein, Amino Acid Sequence, Amino Terminal Sequence, Article, Controlled Study, Enzyme Activation, Enzyme Repression, Human Cell, Liquid Chromatography, Priority Journal, Protein Assembly, Protein Domain, Protein Expression, Protein Motif, Protein Protein Interaction, Tandem Mass Spectrometry, Cell Line, Chemistry, Drug Antagonism, Enzyme Linked Immunosorbent Assay, Genetics, Immunoblotting, Immunoprecipitation, Metabolism, Molecular Genetics, Physiology, Protein Binding, Protein Tertiary Structure, Card Signaling Adaptor Proteins, Enzyme-Linked Immunosorbent Assay, Molecular Sequence Data, Nf-Kappa B, Protein Structure, Nuclear Factor B (nf-B), }, references={Hofmann, K., Bucher, P., Tschopp, J., The CARD domain: A new apoptotic signalling motif (1997) Trends Biochem. 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S., CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF- B activation and apoptosis (1999) J. Biol. Chem, 274, pp. 17946-17954 Ruefli-Brasse, A. A., Lee, W. P., Hurst, S., Dixit, V. M., Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF- B activation (2004) J. Biol. Chem, 279, pp. 1570-1574 Pomerantz, J. L., Denny, E. M., Baltimore, D., CARD11 mediates factor-specific activation of NF- B by the T cell receptor complex (2002) EMBO J, 21, pp. 5184-5194 Jun, J. E., Wilson, L. E., Vinuesa, C. G., Lesage, S., Blery, M., Miosge, L. A., Cook, M. C., Penninger, J. M., Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis (2003) Immunity, 18, pp. 751-762 Grabiner, B. C., Blonska, M., Lin, P. C., You, Y., Wang, D., Sun, J., Darnay, B. G., Lin, X., CARMA3 deficiency abrogates G protein-coupled receptor-induced NF- B activation (2007) Genes Dev, 21, pp. 984-996 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int. J. Pept. Protein Res, 35, pp. 161-214 Vaughn, D. E., Rodriguez, J., Lazebnik, Y., Joshua-Tor, L., Crystal structure of Apaf-1 caspase recruitment domain: An -helical Greek key fold for apoptotic signaling (1999) J. Mol. Biol, 293, pp. 439-447 Richard, J. P., Melikov, K., Vives, E., Ramos, C., Verbeure, B., Gait, M. J., Chernomordik, L. V., Lebleu, B., Cell-penetrating peptides: A reevaluation of the mechanism of cellular uptake (2003) J. Biol. Chem, 278, pp. 585-590 Langel, F. D., Jain, N. A., Rossman, J. S., Kingeter, L. M., Kashyap, A. K., Schaefer, B. C., Multiple protein domains mediate interaction between BCL10 and MALT1 (2008) J. Biol. Chem, 283, pp. 32419-32431}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy Dipartimento di Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone 16, 80134 Napoli, Italy BioGeM Consortium, Via Camporeale, 83031 Ariano Irpino, Italy Centro di Endocrinologia ed Oncologia Sperimentale, 80131 Napoli, Italy Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_9163, author={Viparelli F, Doti N, Sandomenico A, Marasco D, Dathan NA, Miele C, Beguinot F, Monti SM, Ruvo M}, title={GSM48878: CD8 IL2-D2}, date={2011 Dec 2}, journal={Gene Expression Omnibus}, year={2011}, fullvolume={374}, volume={374}, pages={302--308}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-42749089546&partnerID=40&md5=17dd299046dc8eb5c67b73e880bcba43}, abstract={CD8 T cells and B cells were purified from splenocytes subjected to cell culture and activated with 4 ng/ml IL-2full description of sample found in Elena M. Comelli, Mark Sutton-Smith, Qi Yan, Margarida Amado, Maria Panico, Tim Gilmartin, Thomas Whisenant, Caroline M. Lanigan, Steven R. Head, David Goldberg, Howard R. Morris, Anne Dell, and James C. Paulson. (2005). Changes in N-linked Glycosylation of Activated T and B Cells Resulting from Altered Expression of Terminal Glycosyltransferases (in publication).}, keywords={Phospholipase, Phosphoprotein Enriched In Diabetes (ped), Protein-Protein Interaction, Pea15 Protein, Human, Phospholipase D1, Signal Peptide, Article, Biosynthesis, Chemistry, Enzyme Linked Immunosorbent Assay, Genetics, Isolation And Purification, Molecular Cloning, Protein Tertiary Structure, Surface Plasmon Resonance, Enzyme-Linked Immunosorbent Assay, Intracellular Signaling Peptides And Proteins, Protein Structure, }, references={McDermott, M., Wakelam, M.J.O., Morris, A.J., Phospholipase D 1,2, Biochem (2004) Cell Biol., 82, pp. 225-25 Besterman, J.M., Duronio, V., Cuatrecasa, P., Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger (1986) Proc. Natl. Acad. Sci. USA, 83, pp. 6785-6789 Sung, T.C., Zhang, Y., Morris, A.J., Frohman, M.A., Structural analysis of human phospholipase D1 (1999) J. Biol. Chem., 274, pp. 3659-3666 Sung, T.C., Altshuller, Y.M., Morris, A.J., Frohman, M.A., Molecular analysis of mammalian phospholipase D2 (1999) J. Biol. Chem., 274, pp. 494-502 Sung, T.C., Roper, R., Zhang, Y., Rudge, S.A., Temel, R., Hammond, S.M., Morris, A.J., Frohman, M.A., Mutagenesis of Phospholipase D defines a superfamily including a trans-golgi viral protein required for poxvirus pathogenicity (1997) EMBO J., 16, pp. 4519-4539 Stuckey, J.A., Dixon, J.E., Crystal structure of a phospholipase D member (1999) Nat. Struct. Biol., 6, pp. 278-284 Davies, D.R., Interthal, H., Champoux, J.J., Hol, W.G., The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1 (2002) Structure, 10, pp. 237-248 Leiros, I., Secundo, F., Zambonelli, C., Servi, S., Hough, E., The first crystal structure of a phospholipase D (2000) Structure, 8, pp. 655-667 Ponting, C.P., Kerr, I.D., A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues (1996) Protein Sci., 5, pp. 914-922 Xie, Z., Ho, W.T., Exton, J., Association of the N- and C-terminal domains of Phospholipase D (2000) J. Biol. Chem., 275, pp. 24962-24969 Kam, Y., Exton, J.H., Dimerization of phospholipase D isozymes (2002) Biochem. Biophys. Res. Commun., 290, pp. 375-380 Exton, J.H., Phospholipase D-structure, regulation and function (2002) Rev. Physiol. Biochem. Pharmacol., 144, pp. 1-94 Zhang, Y., Redina, O., Altshuller, Y.M., Yamazaki, M., Ramos, J., Chneiweiss, H., Kanaho, Y., Frohman, M.A., Regulation of expression of Phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them (2000) J. Biol. Chem., 275, pp. 35224-35232 Vigliotta, G., Miele, C., Santopietro, S., Portella, G., Perfetti, A., Maitan, M.A., Cassese, A., Beguinot, F., Overexpression of the PED/PEA15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action (2004) Mol. Cell. Biol., 24, pp. 5005-5015 Condorelli, G., Vigliotta, G., Iavarone, C., Caruso, M., Tocchetti, C.G., Andreozzi, F., Cafieri, A., Beguinot, F., PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus (1998) EMBO J., 17, pp. 3858-3866 Xiao, C., Yang, B.F., Asadi, N., Beguinot, F., Hao, C., Tumor necrosis factor-related apoptosis-inducing signaling complex and its modulation by c-Flip and PED/PEA-15 in glioma cells (2002) J. Biol. Chem., 277 (28), pp. 25020-25025 Condorelli, G., Trencia, A., Vigliotta, G., Perfetti, A., Goglia, U., Cassese, A., Musti, A.M., Beguinot, F., Multiple members of the mitogen-activated protein kinase family are necessary for PED/PEA15 anti-apoptotic function (2002) J. Biol. Chem., 277, pp. 11013-11018 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxylmethyl dextran modified gold surface for biospecific interaction analysis in SPR sensors (1991) Anal. Biochem., 198, pp. 268-277 Hill, J.M., Vaidyanathan, H., Ramos, J.W., Ginsberg, M.H., Werner, M.H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) EMBO J., 21, pp. 6494-6504 Besterman, J. M., Duronio, V., Cuatrecasa, P., Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger (1986) Proc. Natl. Acad. Sci. USA, 83, pp. 6785-6789 Sung, T. C., Zhang, Y., Morris, A. J., Frohman, M. A., Structural analysis of human phospholipase D1 (1999) J. Biol. Chem., 274, pp. 3659-3666 Sung, T. C., Altshuller, Y. M., Morris, A. J., Frohman, M. A., Molecular analysis of mammalian phospholipase D2 (1999) J. Biol. Chem., 274, pp. 494-502 Sung, T. C., Roper, R., Zhang, Y., Rudge, S. A., Temel, R., Hammond, S. M., Morris, A. J., Frohman, M. A., Mutagenesis of Phospholipase D defines a superfamily including a trans-golgi viral protein required for poxvirus pathogenicity (1997) EMBO J., 16, pp. 4519-4539 Stuckey, J. A., Dixon, J. E., Crystal structure of a phospholipase D member (1999) Nat. Struct. Biol., 6, pp. 278-284 Davies, D. R., Interthal, H., Champoux, J. J., Hol, W. G., The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1 (2002) Structure, 10, pp. 237-248 Ponting, C. P., Kerr, I. D., A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues (1996) Protein Sci., 5, pp. 914-922 Xie, Z., Ho, W. T., Exton, J., Association of the N- and C-terminal domains of Phospholipase D (2000) J. Biol. Chem., 275, pp. 24962-24969 Kam, Y., Exton, J. H., Dimerization of phospholipase D isozymes (2002) Biochem. Biophys. Res. Commun., 290, pp. 375-380 Exton, J. H., Phospholipase D-structure, regulation and function (2002) Rev. Physiol. Biochem. Pharmacol., 144, pp. 1-94 Xiao, C., Yang, B. F., Asadi, N., Beguinot, F., Hao, C., Tumor necrosis factor-related apoptosis-inducing signaling complex and its modulation by c-Flip and PED/PEA-15 in glioma cells (2002) J. Biol. Chem., 277 (28), pp. 25020-25025 Hill, J. M., Vaidyanathan, H., Ramos, J. W., Ginsberg, M. H., Werner, M. H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) EMBO J., 21, pp. 6494-6504}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134 Napoli, Italy Dipartimento di Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone, 16, 80134 Napoli, Italy Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Via S.M. di Costantinopoli 16, 80138 Napoli, Italy Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS), CNR, Via Pansini, 5, 80131 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_11312, author={Pilla P, Malachovská V, Sandomenico A, Ruvo M, Giordano M, Cutolo A, Cusano A}, title={High Sensitivity Transition-Tuned Long Period Grating For Label-Free Immunosensing}, date={2010}, journal={Proc Spie Int Soc Opt Eng Spie}, year={2010}, fullvolume={189}, volume={189}, pages={76531X--76531X}, url={}, abstract={}, keywords={, }, references={}, document_type={Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_53152, author={Bogdanovich S, Kim Y, Mizutani T, Yasuma R, Tudisco L, Cicatiello V, Bastos-carvalho A, Kerur N, Hirano Y, Baffi JZ, Tarallo V, Li S, Yasuma T, Arpitha P, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ruvo M, Sandomenico A, Nozaki M, Ijima R, Kaneko H, Ogura Y, Terasaki H, Ambati BK, Leusen JH, Langdon WY, Clark MR, Armour KL, Bruhns P, Verbeek JS, Gelfand BD, De Falco S, Ambati J}, title={Human IgG1 antibodies suppress angiogenesis in a target-independent manner}, date={2016}, journal={Signal Transduct Target Ther (ISSN: 2059-3635print)}, year={2016}, fullvolume={528}, volume={528}, pages={N/D--N/D}, url={}, abstract={Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world's population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type and FcγR humanized mice. This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown, Fc cleavage, IgG-Fc inhibition, disruption of Fc-FcγR interaction, or elimination of FcRγ-initated signaling. Furthermore, bevacizumab's Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice. Finally, mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis. These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA., Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan., Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy., Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy; Bio-Ker, MultiMedica Group, Naples, Italy., Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy., Department of Advanced Biomedical Sciences, University of Naples 'Federico II', Naples, Italy; CEINGE-Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy., Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy., Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA., Immunotherapy Laboratory, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia., Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK., Department of Immunology, Unit of Antibodies in Therapy and Pathology, Institut Pasteur, Paris, France; Institut National de la Sante et de la Recherche Medicale (INSERM) U1222, Paris, France., Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Biomedical Engineering}, ibbaffiliation={1}, } @article{IBB_ID_54714, author={Caputo T, Cusano AM, Ruvo M, Aliberti A, Cusano A}, title={Human Serum Albumin Nanoparticles as a Carrier for On-Demand Sorafenib Delivery}, date={2021 Aug 26}, journal={Curr Pharm Biotechnol (ISSN: 1389-2010linking)}, year={2021}, fullvolume={11}, volume={11}, pages={N/D--N/D}, url={}, abstract={BACKGROUND: Drug delivery systems based on Human Serum Albumin (HSA) have been widely investigated due to their capability to interact with several molecules together with their nontoxicity, non-immunogenicity and biocompatibility. Sorafenib (SOR) is a kinase inhibitor used as the first-line treatment in hepatic cancer. However, because of its several intrinsic drawbacks (low solubility and bioavailability), there is a growing need for discovering new carriers able to overcome the current limitations. OBJECTIVE: To study HSA particles loaded with SOR as a thermal responsive drug delivery system. METHOD: A detailed spectroscopy analysis of the HSA and SOR interaction in solution was carried out in order to characterize the temperature dependence of the complex. Based on this study, the synthesis of HSA particles loaded with SOR was optimized. Particles were characterized by Dynamic Light Scattering, Atomic Force Microscopy and by spectrofluorometer. Encapsulation efficiency and in vitro drug release were quantified by RP-HPLC. RESULTS: HSA particles were monodispersed in size (≈ 200 nm); encapsulation efficiency ranged from 25% to 58%. Drug release studies that were performed at 37 °C and 50 °C showed that HS5 particles achieved a drug release of 0.430 µM in 72 hours at 50 °C in PBS buffer, accomplishing a 4.6-fold overall SOR release enhancement following a temperature increase from 37 °C to 50 °C. CONCLUSION: The system herein presented has the potential to exert a therapeutic action (in the nM range) triggering a sustained temperature-controllable release of relevant drugs.}, keywords={Desolvation Technique, Drug Delivery, Human Serum Albumin, Sorafenib, Hepatocellular Carcinoma, Stimuli Responsive Particles}, references={}, document_type={Journal Article}, affiliation={CeRICT scrl Regional Center Information Communication Technology, Benevento. Italy. Institute of Biostructure and Bioimaging, National Research Council, I-80134, Napoli. Italy. Optoelectronics Group, Department of Engineering, University of Sannio, I-82100, Benevento. Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54609, author={Cavalluzzo B, Ragone C, Mauriello A, Petrizzo A, Manolio C, Caporale A, Vitagliano L, Ruvo M, Buonaguro L, Tagliamonte M}, title={Identification and characterization of heteroclitic peptides in TCR-binding positions with improved HLA-binding efficacy}, date={2021 Feb 26}, journal={J Transl Med (ISSN: 1479-5876linking, 1479-5876electronic)}, year={2021}, fullvolume={11}, volume={11}, pages={89--89}, url={}, abstract={The antigenicity as well as the immunogenicity of tumor associated antigens (TAAs) may need to be potentiated in order to break the immunological tolerance. To this aim, heteroclitic peptides were designed introducing specific substitutions in the residue at position 4 (p4) binding to TCR. The effect of such modifications also on the affinity to the major histocompatibility class I (MHC-I) molecule was assessed. The Trp2 antigen, specific for the mouse melanoma B16F10 cells, as well as the HPV-E7 antigen, specific for the TC1 tumor cell lines, were used as models. Affinity of such heteroclitic peptides to HLA was predicted by bioinformatics tools and the most promising ones were validated by structural conformational and HLA binding analyses. Overall, we demonstrated that TAAs modified at the TCR-binding p4 residue are predicted to have higher affinity to MHC-I molecules. Experimental evaluation confirms the stronger binding, suggesting that this strategy may be very effective for designing new vaccines with improved antigenic efficacy.}, keywords={Animals, Antigens, Neoplasm, Hla-A2 Antigen, Mice, Peptides, Protein Binding, Receptors, T-Cell}, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T}, affiliation={Innovative Immunological Models Lab, Istituto Nazionale Tumori "Fond. G. Pascale", Via Mariano Semmola, 1, 80131, Naples, Italy. Institute of Biostructures and Bioimaging, CNR, Naples, Italy. Istituto Di Cristallografia-CNR, c/o area Science Park S.S. 14 Km 163.5 Basovizza, 34149, Trieste, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_10956, author={Doti N, Raimondo D, Sabatella M, Ruvo M}, title={Identification of Protease Inhibitors by a Fast Fluorimetric Assay}, date={2013 Jun}, journal={Mol Biotechnol (ISSN: 1073-6085, 1559-0305electronic, 1073-6085linking)}, year={2013}, fullvolume={389}, volume={389}, pages={283--291}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882899463&partnerID=40&md5=9c7eb53aa1d3b2cfabea02e2e6a6e5a5}, abstract={Anomalous protease activities are associated with many diseases. Great efforts are paid for selecting specific protease modulators for therapeutic approaches. We have selected new modulators of enzyme activity by an homogeneous assay based on a doubly labeled small peptide used as substrate of trypsin. The substrate incorporates the fluorophore 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid (EDANS) at one end and an EDANS-quenching moiety (Dabcyl, (4-(4-dimethylaminophenylazo)-benzoic acid)) on the other end. Following cleavage by trypsin, the peptide-EDANS product is released interrupting the fluorescence resonance energy transfer effect and yielding bright fluorescence, which can be detected using excitation wavelengths at 335-345 nm and emission wavelengths at 485-510 nm. The method optimized, tested by detecting the strong inhibiting effect of alpha 1-antitrypsin on trypsin activity, has been developed on 384 multi-well plates in a volume of 10 mu L, using an automated platform. From the screening of a chemical library, four compounds that inhibit trypsin activity with IC(50)s in the micromolar range have been identified. Interestingly, the most active compound (M4) shows a chemical structure recapitulating that of other more potent inhibitors with thiourea and halogenated centers. Molecular docking studies show that M4 is a competitive inhibitor recognizing most residues within or nearby the catalytic pocket.}, keywords={Fret, Hts, Proteases, Small Molecules, Trypsin Inhibitors, Diagnosis, Energy Transfer, Enzyme Activity, Fluorescence, Naphthalene, Peptides, Enzyme Inhibition, Alpha 1 Antitrypsin, Proteinase Inhibitor, Serine Proteinase, Article, Assay, Chemical Structure, Controlled Study, Excitation, Fluorescence Resonance Energy Transfer, Fluorometry, Ic 50, Molecular Docking, Spectral Sensitivity, Fluorescent Dyes, Naphthalenesulfonates, P-Dimethylaminoazobenzene, Protease Inhibitors, }, references={Heutinck, K.M., Ten Berge, I.J., Hack, C.E., Hamann, J., Rowshani, A.T., Serine proteases of the human immune system in health and disease (2010) Molecular Immunology, 47, pp. 1943-1955. , 10.1016/j.molimm.2010.04.020 1:CAS:528:DC%2BC3cXmvFymtbk%3 Ganesan, R., Eigenbrot, C., Kirchhofer, D., Structural and mechanistic insight into how antibodies inhibit serine proteases (2010) Biochemical Journal, 430, pp. 179-189. , 10.1042/BJ20100634 1:CAS:528:DC%2BC3cXhtVaqsbjF Boris, T., Targeting proteases: Successes, failures and future prospects (2006) Nature Reviews/Drug Discovery, 5, pp. 785-799. , 10.1038/nrd2092 Luo, W., Wang, Y., Reiser, G., Protease-activated receptors in the brain: Receptor expression, activation, and functions in neurodegeneration and neuroprotection (2007) Brain Research Reviews, 56, pp. 331-345. , 10.1016/j.brainresrev.2007.08.002 1:CAS:528:DC%2BD2sXhsVSrsr%2FI Yamauchi, Y., Izumi, Y., Inoue, M., Sugiura, H., Goto, T., Anraku, M., Ohtsuka, T., Nomori, H., Safety of postoperative administration of human urinary trypsin inhibitor in lung cancer patients with idiopathic pulmonary fibrosis (2011) PLoS ONE, 6, p. 29053. , 10.1371/journal.pone.0029053 1:CAS:528:DC%2BC38XltFelsA%3D%3D Ceppa, E.P., Lyo, V., Grady, E.F., Knecht, W., Grahn, S., Peterson, A., Bunnett, N.W., Cattaruzza, F., Serine proteases mediate inflammatory pain in acute pancreatitis (2011) American Journal of Physiology - Gastrointestinal and Liver Physiology, 300, pp. 1033-G1042. , 10.1152/ajpgi.00305.2010 1:CAS:528:DC%2BC3MXot1Cnsb8%3D Katzan, I.L., Furlan, A.J., Lloyd, L.E., Frank, J.I., Harper, D.L., Hinchey, J.A., Hammel, J.P., Sila, C.A., Use of tissue-type plasminogen activator for treatment of acute ischemic stroke: The Cleveland area experience (2000) JAMA, 283, pp. 1151-1158. , 10.1001/jama.283.9.1151 1:CAS:528:DC%2BD3cXhvVent74%3D Shapiro, A.D., Ragni, M.V., Valentino, L.A., Key, N.S., Josephson, N.C., Powell, J.S., Cheng, G., Pierce, G.F., Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients (2011) Blood, 119, pp. 666-672. , 10.1182/blood-2011-07-367003 McLean, C., Greene, C.M., McElvaney, N.G., Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency (2009) Biologics: Targets and Therapy, 3, pp. 1-13 Hayashi, H., Cuddy, M., Shu, V.C.W., Yip, K.W., Madiraju, C., Diaz, P., Matsuyama, T., Reed, J.C., Versatile assays for high throughput screening for activators or inhibitors of intracellular proteases and their cellular regulators (2009) PLoS ONE, 4 (10), pp. 1-18. , 10.1371/journal.pone.0007655 Wang, Y., Luo, W., Reiser, G., Trypsin and trypsin-like proteases in the brain: Proteolysis and cellular functions (2007) Cellular and Molecular Life Sciences, 65, pp. 2237-2252 Zhang, J.H., Chung, T.D., Oldenburg, K.R., A simple statistical parameter for use in evaluation and validation of high throughput screening assays (1999) Journal of Biomolecular Screening, 4, pp. 67-73. , 10.1177/108705719900400206 Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility (2009) Journal Computational Chemistry, 30, pp. 2785-2789. , 10.1002/jcc.21256 1:CAS:528:DC%2BD1MXht1GitrnK Transue, T.R., Gabel, S.A., London, R.E., NMR and crystallographic characterization of adventitious borate binding by trypsin (2006) Bioconjugate Chemistry, 17, pp. 300-308. , 10.1021/bc0502210 1:CAS:528:DC%2BD28Xhs1Ciurk%3D Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., (2004) Journal Computational Chemistry, 25, pp. 1605-1612. , 10.1002/jcc.20084 1:CAS:528:DC%2BD2cXmvVOhsbs%3D Southan, C., Thompson, E., Panico, M., Etienne, T., Morris, H.R., Lane, D.A., Characterization of peptides cleaved by plasmin from the C-terminal polymerization domain of human fibrinogen (1985) Journal of Biological Chemistry, 260, pp. 13095-13101. , 1:CAS:528:DyaL2MXlvFerur4%3D Adibekian, A., Martin, B.R., Wang, C., Hsu, K.L., Bachovchin, D.A., Niessen, S., Hoover, H., Cravatt, B.F., Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors (2011) Nature Chemical Biology, 7, pp. 469-478. , 10.1038/nchembio.579 1:CAS:528:DC%2BC3MXmtV2ht7s%3D Siles, R., Kawasaki, Y., Ross, P., Freire, E., Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases (2011) Bioorganic & Medicinal Chemistry Letters, 21, pp. 5305-5309. , 10.1016/j.bmcl.2011.07.023 1:CAS:528:DC%2BC3MXhtVKis77K Quan, M.L., Ellis, C.D., He, M.Y., Liauw, A.Y., Woerner, F.J., Alexander, R.S., Knabb, R.M., Wexler, R.R., Nonbenzamidine tetrazole derivatives as factor Xa inhibitors (2003) Bioorganic & Medicinal Chemistry Letters, 13, pp. 369-373. , 10.1016/S0960-894X(02)00951-4 1:CAS:528:DC%2BD3sXptFansg%3D%3D Heutinck, K. M., Ten Berge, I. J., Hack, C. E., Hamann, J., Rowshani, A. T., Serine proteases of the human immune system in health and disease (2010) Molecular Immunology, 47, pp. 1943-1955. , 10. 1016/j. molimm. 2010. 04. 020 1: CAS: 528: DC%2BC3cXmvFymtbk%3 Ceppa, E. P., Lyo, V., Grady, E. F., Knecht, W., Grahn, S., Peterson, A., Bunnett, N. W., Cattaruzza, F., Serine proteases mediate inflammatory pain in acute pancreatitis (2011) American Journal of Physiology - Gastrointestinal and Liver Physiology, 300, pp. 1033-G1042. , 10. 1152/ajpgi. 00305. 2010 1: CAS: 528: DC%2BC3MXot1Cnsb8%3D Katzan, I. L., Furlan, A. J., Lloyd, L. E., Frank, J. I., Harper, D. L., Hinchey, J. A., Hammel, J. P., Sila, C. A., Use of tissue-type plasminogen activator for treatment of acute ischemic stroke: The Cleveland area experience (2000) JAMA, 283, pp. 1151-1158. , 10. 1001/jama. 283. 9. 1151 1: CAS: 528: DC%2BD3cXhvVent74%3D Shapiro, A. D., Ragni, M. V., Valentino, L. A., Key, N. S., Josephson, N. C., Powell, J. S., Cheng, G., Pierce, G. F., Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients (2011) Blood, 119, pp. 666-672. , 10. 1182/blood-2011-07-367003 Zhang, J. H., Chung, T. D., Oldenburg, K. R., A simple statistical parameter for use in evaluation and validation of high throughput screening assays (1999) Journal of Biomolecular Screening, 4, pp. 67-73. , 10. 1177/108705719900400206 Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., Olson, A. J., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility (2009) Journal Computational Chemistry, 30, pp. 2785-2789. , 10. 1002/jcc. 21256 1: CAS: 528: DC%2BD1MXht1GitrnK Transue, T. R., Gabel, S. A., London, R. E., NMR and crystallographic characterization of adventitious borate binding by trypsin (2006) Bioconjugate Chemistry, 17, pp. 300-308. , 10. 1021/bc0502210 1: CAS: 528: DC%2BD28Xhs1Ciurk%3D Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., Ferrin, T. E., (2004) Journal Computational Chemistry, 25, pp. 1605-1612. , 10. 1002/jcc. 20084 1: CAS: 528: DC%2BD2cXmvVOhsbs%3D Quan, M. L., Ellis, C. D., He, M. Y., Liauw, A. Y., Woerner, F. J., Alexander, R. S., Knabb, R. M., Wexler, R. R., Nonbenzamidine tetrazole derivatives as factor Xa inhibitors (2003) Bioorganic & Medicinal Chemistry Letters, 13, pp. 369-373. , 10. 1016/S0960-894X (02) 00951-4 1: CAS: 528: DC%2BD3sXptFansg%3D%3D}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, IBB-CNR, Via Mezzocannone 16, 80134 Naples, Italy Department of Physics, Sapienza Università di Roma, P.le Aldo Moro, 5, 00185 Rome, Italy}, ibbaffiliation={1}, } @article{IBB_ID_50555, author={Sandomenico A, Monti SM, Marasco D, Dathan N, Palumbo R, Saviano M, Ruvo M}, title={Ige-Binding Properties And Selectivity Of Peptide Mimics Of The Fcvarepsilonri Binding Site}, date={2009 Oct}, journal={Mol Immunol (ISSN: 0161-5890)}, year={2009}, fullvolume={1612}, volume={1612}, pages={3300--3309}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70349462818&partnerID=40&md5=ab53eae058bf0892271e8cd9906a2822}, abstract={Fc epsilon RI alpha found on the surface of mast cells and basophiles mediates allergic diseases, anaphylaxis and asthma through binding of IgE. Disrupting this interaction with anti-IgE mAbs has proven an efficient approach to control these diseases. The crystallographic structure of the complex formed between the IgE-Fc and Fc epsilon RI alpha extracellular domain has shown that recognition is mediated by residues in the second Ig-like domain of the receptor (132) and in the loop connecting the D1 and D2 domains. In an attempt to obtain specific IgE antagonists, we have designed and prepared a polypeptide named IgE-Trap that partially reproduces the IgE receptor-binding sites and binds with micromolar affinity to soluble IgE. The polypepticle contains loops C'-E [residues 129-134] and F-G [residues 151-1611 from the D2 domain joined by a linker, and loop B-C [residues 110-113]. Peptide binding to IgE has been assessed by SPR analyses and the data fit with a biphasic model of interaction, in agreement with the two-site mechanism reported for the native receptor. The polypeptide binds to immobilized IgE in a dose-dependent manner with a K (D) estimated to be around 6 mu M, while it does not recognize IgG nor IgA. Polypeptide sub-domains involved in IgE binding have also been defined, showing that loop C-E connected to loop B-C, but also the isolated loop B-C alone suffice to bind immunoglobulins E with high selectively though with reduced affinity compared to IgE-Trap. ELISA and cytometric assays on RBL2H3 cells demonstrate that the interacting peptides are able to displace the binding of IgE to receptor, confirming affinity and specificity of these ligands and suggesting a potential application as modulators of disorders associated with inappropriate IgE production. (C) 2009 Elsevier Ltd. All rights reserved}, keywords={Elisa, Fcεri, Peptide Mimics, Fc Receptor, Immunoglobulin A, Immunoglobulin E Receptor, Immunoglobulin E Trap, Polypeptide, Unclassified Drug, Animal Cell, Article, Binding Affinity, Binding Competition, Binding Site, Biotinylation, Concentration Response, Controlled Study, Enzyme Linked Immunosorbent Assay, Flow Cytometry, Immunoglobulin Production, Nonhuman, Peptide Synthesis, Priority Journal, Protein Binding, Protein Domain, Surface Plasmon Resonance, Cell Line, Hypersensitivity, Ligands, Protein Structure, Secondary, Tertiary, }, references={Ames, S.A., Gleeson, C.D., Kirkpatrick, P., Omalizumab (2004) Nat. Rev. Drug Discov., 3, pp. 199-20 Basu, M., Hakimi, J., Dharm, E., Kondas, J.A., Tsien, W.H., Pilson, R.S., Lin, P., Braswell, E.H., Purification and characterization of human recombinant IgE-Fc fragments that bind to the human high affinity IgE receptor (1993) J. Biol. 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Chem., 46, pp. 3008-3012 Buku, A., Price, J.A., Mendlowitz, M., Masur, S., Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors and inhibits IgE binding (2001) Peptides, 22, pp. 1993-1998 Cook, J.P., Henry, A.J., McDonnell, J.M., Owens, R.J., Sutton, B.J., Gould, H.J., Identification of contact residues in the IgE binding site of human FcepsilonRIalpha (1997) Biochemistry, 36, pp. 15579-15588 Cookson, W., The alliance of gene and environmental in asthma and allergy (1999) Nature, 402, pp. 5-11 Corren, J., Casale, T.B., Lanier, B., Buhl, R., Holgate, S., Jimenez, P., Safety and tolerability of omalizumab (2009) Clin. Exp. Allergy Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Garman, S.C., Kinet, J.P., Jardetzky, T.S., Crystal structure of the human high-affinity IgE receptor (1998) Cell, 95, pp. 951-961 Garman, S.C., Sechi, S., Kinet, J.P., Jardetzky, T.S., The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms (2001) J. Mol. Biol., 311, pp. 1049-1062 Garman, S.C., Wurzburg, B.A., Tarchevskaya, S.S., Kinet, J.P., Jardetzky, T.S., Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha (2000) Nature, 406, pp. 259-266 Henry, A.J., Cook, J.P., McDonnell, J.M., Mackay, G.A., Shi, J., Sutton, B.J., Gould, H.J., Participation of the N-terminal region of Cepsilon3 in the binding of human IgE to its high-affinity receptor FcepsilonRI (1997) Biochemistry, 36, pp. 15568-15578 Jardieu, P., Anti-IgE therapy (1995) Curr. Opin. 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S., The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms (2001) J. Mol. Biol., 311, pp. 1049-1062 Garman, S. C., Wurzburg, B. A., Tarchevskaya, S. S., Kinet, J. P., Jardetzky, T. S., Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha (2000) Nature, 406, pp. 259-266 Henry, A. J., Cook, J. P., McDonnell, J. M., Mackay, G. A., Shi, J., Sutton, B. J., Gould, H. J., Participation of the N-terminal region of Cepsilon3 in the binding of human IgE to its high-affinity receptor FcepsilonRI (1997) Biochemistry, 36, pp. 15568-15578 Kinet, J. P., The high-affinity receptor for IgE (1989) Curr. Opin. Immunol., 2, pp. 499-505 McDonnell, J. M., Beavil, A. J., Mackay, G. A., Henry, A. J., Cook, J. P., Gould, H. J., Sutton, B. J., Structure-based design of peptides that inhibit IgE binding to its high-affinity receptor Fc epsilon RI (1997) Biochem. Soc. Trans., 25, pp. 387-392 McDonnell, J. M., Calvert, R., Beavil, R. L., Beavil, A. J., Henry, A. J., Sutton, B. J., Gould, H. J., Cowburn, D., The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its high-affinity receptor FcepsilonRIalpha (2001) Nat. Struct. Biol., 8, pp. 437-441 Meltzer, E. O., Grant, J. A., Impact of cetirizine on the burden of allergic rhinitis (1999) Ann. Allergy Asthma Immunol., 83, pp. 455-463 Nakamura, G. R., Reynolds, M. E., Chen, Y. M., Starovasnik, M. A., Lowman, H. B., Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor (2002) Proc. Natl. Acad. Sci. U. S. A., 99, pp. 1303-1308 Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E., Lowman, H. B., A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor (2001) Biochemistry, 40, pp. 9828-9835 Rigby, L. J., Epa, V. C., Mackay, G. A., Hulett, M. D., Sutton, B. J., Gould, H. J., Hogarth, P. M., Domain one of the high affinity IgE receptor, FcepsilonRI, regulates binding to IgE through its interface with domain two (2000) J. Biol. Chem., 275, pp. 9664-9672 Rigby, L. J., Trist, H., Snider, J., Hulett, M. D., Hogarth, P. M., Epa, V. C., Monoclonal antibodies and synthetic peptides define the active site of FcepsilonRI and a potential receptor antagonist (2000) Allergy, 55, pp. 609-619 Scharenberg, A. M., Lin, S., Cuenod, B., Yamamura, H., Kinet, J. P., Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering (1995) Embo J., 14, pp. 3385-3394}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134 Napoli, Italy Dipartimento delle Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10736, author={Nold-Petry CA, Rudloff I, Baumer Y, Ruvo M, Marasco D, Botti P, Farkas L, Cho SX, Zepp JA, Azam T, Dinkel H, Palmer BE, Boisvert WA, Cool CD, Taraseviciene-Stewart L, Heinhuis B, Joosten LA, Dinarello CA, Voelkel NF, Nold MF}, title={IL-32 Promotes Angiogenesis}, date={2014 Jan 15}, journal={J Immunol (ISSN: 0022-1767)}, year={2014}, fullvolume={660}, volume={660}, pages={589--602}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84892700407&partnerID=40&md5=a21cccfae6647aeac2ed898eb859caea}, abstract={IL-32 is a multifaceted cytokine with a role in infections, autoimmune diseases, and cancer, and it exerts diverse functions, including aggravation of inflammation and inhibition of virus propagation. We previously identified IL-32 as a critical regulator of endothelial cell (EC) functions, and we now reveal that IL-32 also possesses angiogenic properties. The hyperproliferative ECs of human pulmonary arterial hypertension and glioblastoma multiforme exhibited a markedly increased abundance of IL-32, and, significantly, the cytokine colocalized with integrin alpha v beta(3). Vascular endothelial growth factor (VEGF) receptor blockade, which resulted in EC hyperproliferation, increased IL-32 three-fold. Small interfering RNA-mediated silencing of IL-32 negated the 58% proliferation of ECs that occurred within 24 h in scrambled-transfected controls. Reduction of IL-32 neither affected apoptosis (insignificant changes in Bak-1, Bcl-2, Bcl-x(L), lactate dehydrogenase, annexin V, and propidium iodide) nor VEGF or TGF-beta levels, but siIL-32-transfected adult and neonatal ECs produced up to 61% less NO, IL-8, and matrix metalloproteinase-9, and up to 3-fold more activin A and endostatin. In coculture-based angiogenesis assays, IL-32 gamma dose-dependently increased tube formation up to 3-fold; an alpha v beta(3) inhibitor prevented this activity and reduced IL-32 gamma-induced IL-8 by 85%. In matrigel plugs loaded with IL-32 gamma, VEGF, or vehicle and injected into live mice, we observed the anticipated VEGF-induced increase in neocapillarization (8-fold versus vehicle), but unexpectedly, IL-32 gamma was equally angiogenic. A second signal such as IFN-gamma was required to render cells responsive to exogenous IL-32 gamma; importantly, this was confirmed using a completely synthetic preparation of IL-32 gamma. In summary, we add angiogenic properties that are mediated by integrin alpha v beta(3) but VEGF-independent to the portfolio of IL-32, implicating a role for this versatile cytokine in pulmonary arterial hypertension and neoplastic diseases.}, keywords={Activin A, Endostatin, Gamma Interferon, Gelatinase B, Interleukin 32, Interleukin 32gamma, Lactate Dehydrogenase, Nitric Oxide, Protein Bak, Protein Bcl 2, Semaxanib, Small Interfering Rna, Transforming Growth Factor Beta, Unclassified Drug, Vasculotropin, Vasculotropin Receptor, Vitronectin Receptor, Adult, Animal Experiment, Animal Tissue, Apoptosis, Article, Cell Proliferation, Cellular Distribution, Coculture, Concentration Response, Controlled Study, Glioblastoma, Human, Human Cell, Human Tissue, Microvascular Endothelial Cell, Mouse, Neovascularization (pathology), Newborn, Nonhuman, Priority Journal, Pulmonary Hypertension, Umbilical Vein Endothelial Cell, Human Umbilical Vein Endothelial Cells, Integrin Alphavbeta3, Interferon-Gamma, Matrix Metalloproteinase 9, Nitrogen Oxides, Vascular Endothelial Growth Factor, }, references={Kim, S.H., Han, S.Y., Azam, T., Yoon, D.Y., Dinarello, C.A., Interleukin-32: A cytokine and inducer of TNFa (2005) Immunity, 22, pp. 131-14 Goda, C., Kanaji, T., Kanaji, S., Tanaka, G., Arima, K., Ohno, S., Izuhara, K., Involvement of IL-32 in activation-induced cell death in T cells (2006) International Immunology, 18 (2), pp. 233-240. , DOI 10.1093/intimm/dxh339 Imaeda, H., Andoh, A., Aomatsu, T., Osaki, R., Bamba, S., Inatomi, O., Shimizu, T., Fujiyama, Y., A new isoform of interleukin-32 suppresses IL-8 mRNA expression in the intestinal epithelial cell line HT-29 (2011) Mol Med Rep, 4, pp. 483-487 Nold-Petry, C.A., Nold, M.F., Zepp, J.A., Kim, S.H., Voelkel, N.F., Dinarello, C.A., IL-32-dependent effects of IL-1β on endothelial cell functions (2009) Proc. 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L., Focal adhesion kinase inhibitors are potent anti-angiogenic agents (2011) Mol. Oncol., 5, pp. 517-526 Shen, T. -L., Park, A. Y. -J., Alcaraz, A., Peng, X., Jang, I., Koni, P., Flavell, R. A., Guan, J. -L., Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis (2005) Journal of Cell Biology, 169 (6), pp. 941-952. , http: //www. jcb. org/cgi/reprint/169/6/941. pdf, DOI 10. 1083/jcb. 200411155 Nisato, R. E., Tille, J. -C., Jonczyk, A., Goodman, S. L., Pepper, M. S., v 3 and v 5 integrin antagonists inhibit angiogenesis in vitro (2003) Angiogenesis, 6 (2), pp. 105-119. , DOI 10. 1023/B: AGEN. 0000011801. 98187. f2 Cho, K. A., Jun, Y. H., Suh, J. W., Kang, J. S., Choi, H. J., Woo, S. Y., Orientia tsutsugamushi induced endothelial cell activation via the NOD1-IL-32 pathway (2010) Microb. Pathog., 49, pp. 95-104}, document_type={Journal Article, }, affiliation={Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, VIC 3168, Australia Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerce, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, 80134 Naples, Italy Department of Pharmacy, University of Naples Federico II, 80134 Naples, Italy ArisGen SA, 1228 Plan-les-Ouates, Switzerland Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States Department of Medicine, University of Colorado Denver, Aurora, CO 80045, United States Department of Pathology, University of Colorado Denver, Aurora, CO 80045, United States Radboud University Medical Center, 6500 HB Nijmegen, Netherlands Pulmonary and Critical Care Medicine Division, Molecular Medicine Research Building, Virginia Commonwealth University, Broad Street, Richmond, VA 23298, United States}, ibbaffiliation={1}, } @article{IBB_ID_53947, author={Mercurio L, Morelli M, Scarponi C, Eisenmesser EZ, Doti N, Pagnanelli G, Gubinelli E, Mazzanti C, Cavani A, Ruvo M, Dinarello CA, Albanesi C, Madonna S}, title={IL-38 has an anti-inflammatory action in psoriasis and its expression correlates with disease severity and therapeutic response to anti-IL-17A treatment}, date={2018 Oct 30}, journal={Cell Death & (ISSN: 2041-4889electronic)}, year={2018}, fullvolume={201}, volume={201}, pages={1104--1104}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055620182&doi=10.1038%2fs41419-018-1143-3&partnerID=40&md5=f7e3fe595237c93b34ba1cbedc115770}, abstract={IL-36 cytokines, a subgroup of IL-1 family, comprise IL-36alpha, IL-36beta, and IL-36gamma agonists, abundantly expressed in psoriatic skin, and IL-36RA and IL-38 antagonists. In psoriatic skin, IL-36 cytokines interfere with keratinocyte cornification programs and induce the release of antimicrobial peptides and chemokines active on neutrophils and Th17 lymphocytes. To date, the role of IL-38 antagonist in psoriasis remains to be defined. Here, we demonstrate that skin and circulating IL-38 levels are reduced in psoriatic patients and in other skin diseases characterized by neutrophilic infiltrate. In psoriasis, the balance of IL-36gamma agonist/IL-38 antagonist serum levels is in favor of agonists and is closely associated with disease severity. Interestingly, IL-38 is upregulated by anti-IL-17A biological treatment and positively correlates with the therapeutic efficacy of secukinumab in psoriatic patients. The downregulation of IL-38 expression is strictly related to keratinocyte de-differentiation triggered by the inflammatory cytokines IL-36gamma, IL-17, and IL-22. Finally, we demonstrate that administration of recombinant full-length IL-38 counteracts in vitro the biological processes induced by IL-36gamma in human keratinocytes and endothelial cells and attenuates in vivo the severity of the psoriasiform phenotype induced by IMQ in mice. Such effects are achieved by restoring the physiological programs of keratinocyte proliferation and differentiation, and reducing the immune cell infiltrates.}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={Laboratory of Experimental Immunology and Integrated Research Center for PSOriasis (CRI-PSO), Istituto Dermopatico dell'Immacolata IDI-IRCCS, via Monti di Creta, 104, ROME, Italy., Section of Dermatology, Department of Medicine, University of Verona, P.zza Stefani, 1, Verona, 37126, Italy., Department of Biochemistry & Molecular Genetics, School of Medicine, University of Colorado Denver, Anschutz Campus, Aurora, 80045, CO, USA., Istituto di Biostrutture e Bioimmagini-CNR and CIRPEB, Via Mezzocannone, 16, Naples, 80134, Italy., 1st Division of Dermatology and CRI-PSO, Istituto Dermopatico dell'Immacolata IDI-IRCCS, via Monti di Creta, 104, Rome, 00167, Italy., CRI-PSO Istituto Dermopatico dell'Immacolata, IDI-IRCCS, via Monti di Creta, 104, Rome, 00167, Italy., INMP/NIHMP, via di S.Gallicano, 25, Rome, 00153, Italy., Department of Medicine, Radboud University Medical Center, 6525 HP, Nijmegen, The Netherlands., Department of Medicine, School of Medicine, University of Colorado, Denver, Anschutz Campus, Aurora, CO, USA., Laboratory of Experimental Immunology and Integrated Research Center for PSOriasis (CRI-PSO), Istituto Dermopatico dell'Immacolata IDI-IRCCS, via Monti di Creta, 104, ROME, Italy. s.madonna@idi.it., via di S.Gallicano ,25, Rome, 00153, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54322, author={Caporale A, Bolzati C, Incisivo GM, Salvarese N, Grieco P, Ruvo M}, title={Improved synthesis on solid phase of dithiocarbamic cRGD-derivative and (99m) Tc-radiolabelling}, date={2019 Feb}, journal={J Pept Sci (ISSN: 1075-2617linking, 1099-1387electronic)}, year={2019}, fullvolume={181}, volume={181}, pages={e3140--e3140}, url={}, abstract={In the field of angiogenesis, small cyclic pentapeptides containing the RGD motif are playing a relevant role for their high affinity and specificity for integrin receptors and for the possibility to act at both therapeutic and diagnostic level by inhibiting pathological angiogenesis and by serving as shuttles to deliver imaging-probe including SPECT/PET radionuclides to specific tissues. In the last decade, several new protocols were reported in literature for the direct synthesis of cyclic RDG either in solution or by SPPS. Here, we have elaborated and tested some alternative approaches using different resins and different protective groups. The introduction of the dithiocarbamate function, useful to complex radio-metals suitable for nuclear medicine applications, has also been considered and achieved.}, keywords={Molecular Conformation, Oligopeptides, Chemical Synthesis, Chemistry, Radiopharmaceuticals, Technetium, Thiocarbamates, Nuclear Medicine, On-Resin Functionalization, Radionuclide, }, references={}, document_type={Journal Article, }, affiliation={IBB-CNR, Naples, 80134, Italy., Univ. di Napoli "Federico II", CIRPeB, Naples, 80134, Italy., ICMATE-CNR Padova, Padova, 35127, Italy., Dept. Pharmacy, Univ. di Napoli "Federico II", Naples, 80131, Italy., }, ibbaffiliation={1}, } @article{IBB_ID_53946, author={Caporale A, Bolzati C, M, Incisivo G, Salvarese N, Grieco P, Ruvo M}, title={Improved synthesis on SPPS of dithiocarbamic cRGD-derivative and its application in 99mTc-radiolabelling}, date={2018}, journal={Peptide Science}, year={2018}, fullvolume={303}, volume={303}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_10958, author={Doti N, Reuther C, Scognamiglio PL, Dolga AM, Plesnila N, Ruvo M, Culmsee C}, title={Inhibition of the AIF/CypA complex protects against intrinsic death pathways induced by oxidative stress}, date={2014 Jan 16}, journal={Cell Death & (ISSN: 2041-4889, 2041-4889electronic)}, year={2014}, fullvolume={531}, volume={531}, pages={e993--e993}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84891783666&partnerID=40&md5=a53c824ae1c04cb0100246b242c5ca34}, abstract={Delayed neuronal cell death largely contributes to the progressive infarct development and associated functional impairments after cerebral ischemia or brain trauma. Previous studies exposed a key role for the interaction of the mitochondrial protein apoptosis-inducing factor (AIF) and cytosolic cyclophilin A (CypA) in pathways of programmed cell death in neurons in vitro and in vivo. These studies suggested that pro-apoptotic activities of AIF, such as its translocation to the nucleus and subsequent DNA degradation, depend on the physical interaction of AIF with CypA. Hence, this protein complex may represent a new pharmacological target for inhibiting the lethal action of AIF on the brain tissue. In this study, we show that the AIF amino-acid residues 370-394 mediate the protein complex formation of AIF with CypA. The synthetic AIF(370-394) peptide inhibited AIF/CypA complex formation in vitro by binding CypA with a KD of 12 μM. Further, the peptide exerted pronounced neuroprotective effects in a model of glutamate-induced oxidative stress in cultured HT-22 cells. In this model system of AIF-dependent cell death, the AIF(370-394) peptide preserved mitochondrial integrity, as detected by measurements of the mitochondrial membrane potential and quantification of mitochondrial fragmentation. Further, the AIF(370-394) peptide inhibited perinuclear accumulation of fragmented mitochondria, mitochondrial release of AIF to the nucleus and glutamate-induced cell death to a similar extent as CypA-siRNA. These data indicate that the targeting of the AIF-CypA axis is an effective strategy of neuroprotection. © 2014 Macmillan Publishers Limited.}, keywords={Aif Cypa Complex, Mitochondria, Neuronal Death, Oxidative Stress, Peptide Inhibitor, Apoptosis Inducing Factor, Calcium Ion, Cyclophilin A, Glutamic Acid, Small Interfering Rna, Article, Cell Survival, Complex Formation, Controlled Study, In Vitro Study, Intracellular Signaling, Mitochondrial Membrane Potential, Nerve Cell Necrosis, Neuroprotection, Priority Journal, Protein Binding, Protein Expression, Protein Protein Interaction, Protein Secretion, Protein Transport, Amino Acid Motifs, Down-Regulation, Humans, Apoptosis Inducing Factor Chemistry Genetics Metabolism, Cyclophilin A Genetics Metabolism, Mitochondria Enzymology Metabolism, Neurons Cytology Enzymology Metabolism, }, references={Hangen, E., Blomgren, K., Bénit, P., Kroemer, G., Modjtahedi, N., Life with or without AIF (2010) Trends Biochem Sci, 35, pp. 278-28 Sevrioukova, I.F., Apoptosis-inducing factor: Structure, function, and redox regulation (2011) Antioxid Redox Signal, 14, pp. 2545-2579 Polster, B.M., AIF, reactive oxygen species, and neurodegeneration: A "complex" problem (2013) Neurochem Int, 62, pp. 695-702 Vahsen, N., Candéc, Brière, J.J., Bénit, P., Joza, N., Larochette, N., AIF deficiency compromises oxidative phosphorylation (2004) EMBO J, 23, pp. 4679-4689 Cheung, E.C., Joza, N., Steenaart, N.A., McClellan, K.A., Neuspiel, M., McNamara, S., Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis (2006) EMBO J, 25, pp. 4061-4073 Cao, G., Clark, R.S., Pei, W., Yin, W., Zhang, F., Sun, F.Y., Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation (2003) J Cereb Blood Flow Metab, 23, pp. 1137-1150 Pallast, S., Arai, K., Pekcec, A., Yigitkanli, K., Yu, Z., Wang, X., Increased nuclear apoptosisinducing factor after transient focal ischemia: A 12/15-lipoxygenase-dependent organelle damage pathway (2010) J Cereb Blood Flow Metab, 30, pp. 1157-1167 Plesnila, N., Zhu, C., Culmsee, C., Gröger, M., Moskowitz, M.A., Blomgren, K., Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia (2004) J Cereb Blood Flow Metab, 24, pp. 458-466 Thal, S.E., Zhu, C., Thal, S.C., Blomgren, K., Plesnila, N., Role of apoptosis inducing factor (AIF) for hippocampal neuronal cell death following global cerebral ischemia in mice (2011) Neurosci Lett, 499, pp. 1-3 Culmsee, C., Zhu, C., Landshamer, S., Becattini, B., Wagner, E., Pellecchia, M., Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia (2005) J Neuroscience, 25, pp. 10262-10272 Slemmer, J.E., Zhu, C., Landshamer, S., Trabold, R., Grohm, J., Ardeshiri, A., Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury (2008) Am J Pathol, 173, pp. 1795-1805 Piao, C.S., Loane, D.J., Stoica, B.A., Li, S., Hanscom, M., Cabatbat, R., Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury (2012) Neurobiol Dis, 46, pp. 745-758 Candé, C., Vahsen, N., Kouranti, I., Schmitt, E., Daugas, E., Spahr, C., AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis (2004) Oncogene, 23, pp. 1514-1521 Zhu, C., Wang, X., Deinum, J., Huang, Z., Gao, J., Modjtahedi, N., Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxiaischemia (2007) J Exp Med, 204, pp. 1741-1748 Handschumacher, R.E., Harding, M.W., Rice, J., Drugge, R.J., Speicher, D.W., Cyclophilin: A specific cytosolic binding protein for cyclosporin A (1984) Science, 226, pp. 544-547 Goldner, F.M., Patrick, J.W., Neuronal localization of the cyclophilin A protein in the adult rat brain (1996) J Comp Neurol, 372, pp. 283-293 Montague, J.W., Hughes Jr., F.M., Cidlowski, J.A., Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cis-trans-isomerase activity. Potential roles of cyclophilins in apoptosis (1997) J Biol Chem, 272, pp. 6677-6684 Zhang, X.C., Wang, W.D., Wang, J.S., Pan, J.C., PPIase independent chaperone-like function of recombinant human Cyclophilin A during arginine kinase refolding (2013) FEBS Lett, 587, pp. 666-672 Gurbuxani, S., Schmitt, E., Cande, C., Parcellier, A., Hammann, A., Daugas, E., Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor (2003) Oncogene, 22, pp. 6669-6678 Fukui, M., Song, J.H., Choi, J., Choi, H.J., Zhu, B.T., Mechanism of glutamate-induced neurotoxicity in HT22 mouse hippocampal cells (2009) Eur J Pharmacol, 617, pp. 1-11 Artus, C., Boujrad, H., Bouharrour, A., Brunelle, M.N., Hoos, S., Yuste, V.J., AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX (2010) EMBO J, 29, pp. 1585-1599 Guo, X., Surface plasmon resonance based biosensor technique: A review (2012) J Biophotonics, 5, pp. 483-501 Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, B.E., Brothers, G.M., Molecular characterization of mitochondrial apoptosis-inducing factor (1999) Nature, 397, pp. 441-446 Ke, H., Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63A resolution (1992) J Mol Biol, 228, pp. 539-550 Grohm, J., Plesnila, N., Culmsee, C., Bid mediates fission, membrane permeabilization and perinuclear accumulation of mitochondria as a prerequisite for oxidative neuronal cell death (2010) Brain Behav Immun, 24, pp. 831-838 Grohm, J., Kim, S.W., Mamrak, U., Tobaben, S., Cassidy-Stone, A., Nunnari, J., Inhibition of Drp1 provides neuroprotection in vitro and in vivo (2012) Cell Death Differ, 19, pp. 1446-1458 Petit, P.X., Susin, S.A., Zamzami, N., Mignotte, B., Kroemer, G., Mitochondria and programmed cell death: Back to the future (1996) FEBS Lett, 396, pp. 7-13 Tobaben, S., Grohm, J., Seiler, A., Conrad, M., Plesnila, N., Culmsee, C., Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons (2011) Cell Death Differ, 18, pp. 282-292 Smiley, S.T., Reers, M., Mottola-Hartshorn, C., Lin, M., Chen, A., Smith, T.W., Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1 (1991) Proc Natl Acad Sci USA, 88, pp. 3671-3675 Xu, J., Hao, Z., Gou, X., Tian, W., Jin, Y., Cui, S., Imaging of reactive oxygen species burst from mitochondria using laser scanning confocal microscopy (2013) Microsc Res Tech, 76, pp. 612-617 Pinton, P., Giorgi, C., Siviero, R., Zecchini, E., Rizzuto, R., Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis (2008) Oncogene, 27, pp. 6407-6418 Utkina-Sosunova, I.V., Niatsetskaya, Z.V., Sosunov, S.A., Ratner, V.I., Matsiukevich, D., Ten, V.S., Nelfinavir inhibits intra-mitochondrial calcium influx and protects brain against hypoxicischemic injury in neonatal mice (2013) PLoS One, 8, pp. e62448 Cao, G., Xing, J., Xiao, X., Liou, A.F.K., Yin, X.M., Clark, R.S.B., Critical role of calpain i in mitochondrial release of apoptosis-inducing factor in ischemic neuronal injury (2007) J Neurosci, 27, pp. 9278-9293 Wang, P., Heitman, J., The cyclophilins (2005) Genome Biol, 6, p. 226 Yu, S.W., Wang, Y., Frydenlund, D.S., Ottersen, O.P., Dawson, V.L., Dawson, T.M., Outer mitochondrial membrane localization of apoptosis-inducing factor: Mechanistic implications for release (2009) ASN Neuro, 1, pp. e00021 Tremper-Wells, B., Vallano, M.L., Nuclear calpain regulates Ca2+-dependent signaling via proteolysis of nuclear Ca2+/calmodulin-dependent protein kinase type IV in cultured neurons (2005) J Biol Chem, 280, pp. 2165-2175 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Johnsson, B., Lofas, S., Lindquist, G., Immobilization of proteins to a carboxymethyldextran modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors (1991) Anal Biochem, 198, pp. 268-277 Dolga, A.M., Letsche, T., Gold, M., Doti, N., Bacher, M., Chiamvimonvat, N., Activation of KCNN3/SK3/K(Ca) 2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia (2012) Glia, 60, pp. 2050-2064 Myszka, D.G., Analysis of small-molecule interactions using Biacore S51 technology (2004) Anal Biochem, 329, pp. 316-323 Diemert, S., Dolga, A.M., Tobaben, S., Grohm, J., Pfeifer, S., Oexler, E., Impedance measurement for real time detection of neuronal cell death (2012) J Neurosci Methods, 203, pp. 69-77 Öxler, E.M., Dolga, A., Culmsee, C., AIF depletion provides neuroprotection through a preconditioning effect (2012) Apoptosis, 17, pp. 1027-1038 Sevrioukova, I. F., Apoptosis-inducing factor: Structure, function, and redox regulation (2011) Antioxid Redox Signal, 14, pp. 2545-2579 Polster, B. M., AIF, reactive oxygen species, and neurodegeneration: A "complex" problem (2013) Neurochem Int, 62, pp. 695-702 Vahsen, N., Cand c, Bri re, J. J., B nit, P., Joza, N., Larochette, N., AIF deficiency compromises oxidative phosphorylation (2004) EMBO J, 23, pp. 4679-4689 Cheung, E. C., Joza, N., Steenaart, N. A., McClellan, K. A., Neuspiel, M., McNamara, S., Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis (2006) EMBO J, 25, pp. 4061-4073 Cao, G., Clark, R. S., Pei, W., Yin, W., Zhang, F., Sun, F. Y., Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation (2003) J Cereb Blood Flow Metab, 23, pp. 1137-1150 Thal, S. E., Zhu, C., Thal, S. C., Blomgren, K., Plesnila, N., Role of apoptosis inducing factor (AIF) for hippocampal neuronal cell death following global cerebral ischemia in mice (2011) Neurosci Lett, 499, pp. 1-3 Slemmer, J. E., Zhu, C., Landshamer, S., Trabold, R., Grohm, J., Ardeshiri, A., Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury (2008) Am J Pathol, 173, pp. 1795-1805 Piao, C. S., Loane, D. J., Stoica, B. A., Li, S., Hanscom, M., Cabatbat, R., Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury (2012) Neurobiol Dis, 46, pp. 745-758 Cand, C., Vahsen, N., Kouranti, I., Schmitt, E., Daugas, E., Spahr, C., AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis (2004) Oncogene, 23, pp. 1514-1521 Handschumacher, R. E., Harding, M. W., Rice, J., Drugge, R. J., Speicher, D. W., Cyclophilin: A specific cytosolic binding protein for cyclosporin A (1984) Science, 226, pp. 544-547 Goldner, F. M., Patrick, J. W., Neuronal localization of the cyclophilin A protein in the adult rat brain (1996) J Comp Neurol, 372, pp. 283-293 Montague, J. W., Hughes Jr., F. M., Cidlowski, J. A., Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cis-trans-isomerase activity. Potential roles of cyclophilins in apoptosis (1997) J Biol Chem, 272, pp. 6677-6684 Zhang, X. C., Wang, W. D., Wang, J. S., Pan, J. C., PPIase independent chaperone-like function of recombinant human Cyclophilin A during arginine kinase refolding (2013) FEBS Lett, 587, pp. 666-672 Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Molecular characterization of mitochondrial apoptosis-inducing factor (1999) Nature, 397, pp. 441-446 Grohm, J., Kim, S. W., Mamrak, U., Tobaben, S., Cassidy-Stone, A., Nunnari, J., Inhibition of Drp1 provides neuroprotection in vitro and in vivo (2012) Cell Death Differ, 19, pp. 1446-1458 Petit, P. X., Susin, S. A., Zamzami, N., Mignotte, B., Kroemer, G., Mitochondria and programmed cell death: Back to the future (1996) FEBS Lett, 396, pp. 7-13 Smiley, S. T., Reers, M., Mottola-Hartshorn, C., Lin, M., Chen, A., Smith, T. W., Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1 (1991) Proc Natl Acad Sci USA, 88, pp. 3671-3675 Yu, S. W., Wang, Y., Frydenlund, D. S., Ottersen, O. P., Dawson, V. L., Dawson, T. M., Outer mitochondrial membrane localization of apoptosis-inducing factor: Mechanistic implications for release (2009) ASN Neuro, 1, pp. e00021 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214 Dolga, A. M., Letsche, T., Gold, M., Doti, N., Bacher, M., Chiamvimonvat, N., Activation of KCNN3/SK3/K (Ca) 2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia (2012) Glia, 60, pp. 2050-2064 Myszka, D. G., Analysis of small-molecule interactions using Biacore S51 technology (2004) Anal Biochem, 329, pp. 316-323 xler, E. M., Dolga, A., Culmsee, C., AIF depletion provides neuroprotection through a preconditioning effect (2012) Apoptosis, 17, pp. 1027-1038}, document_type={Abstract, Conference, Research Support, Non-U. S. Gov'T, }, affiliation={Institute of Biostructures and Bioimaging (IBB), CNR, CIRPEB, Via Mezzocannone, 16, Naples 80134, Italy Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Karl-von-Frisch-Straße 1, Marburg 35032, Germany Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland Institute for Stroke and Dementia Research (ISD), University of Munich Medical School-Campus Großhadern, Max-Lebsche Platz 30, Munich 81377, Germany 1] Institute of Biostructures and Bioimaging (IBB)-CNR, CIRPEB, Via Mezzocannone, 16, Naples 80134, Italy [2] Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Marburg 35032, Germany [3] Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 1] Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland [2] Institute for Stroke and Dementia Research (ISD), University of Munich Medical School-Campus Grosshadern, Max-Lebsche Platz 30, Munich D-81377, Germany.}, ibbaffiliation={1}, } @article{IBB_ID_50996, author={Papa S, Monti SM, Vitale RM, Bubici C, Jayawardena S, Alvarez K, De Smaele E, Dathan N, Pedone C, Ruvo M, Franzoso G}, title={Insights Into The Structural Basis Of The Gadd45beta-Mediated Inactivation Of The Jnk Kinase, Mkk7/Jnkk2}, date={2007 Jun 29}, journal={Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking)}, year={2007}, fullvolume={441}, volume={441}, pages={19029--19041}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547102525&partnerID=40&md5=f680be8dde6612ac7aedbc4be68f8084}, abstract={NF-κB/Rel factors control programmed cell death (PCD), and this control is crucial to oncogenesis, cancer chemoresistance, and antagonism of tumor necrosis factor (TNF) α-induced killing. With TNFα, NF-κB-mediated protection involves suppression of the c-Jun-N-terminal kinase (JNK) cascade, and we have identified Gadd45β, a member of the Gadd45 family, as a pivotal effector of this activity of NF-κB. Inhibition of TNFα-induced JNK signaling by Gadd45β depends on direct targeting of the JNK kinase, MKK7/JNKK2. The mechanism by which Gadd45β blunts MKK7, however, is unknown. Here we show that Gadd45β is a structured protein with a predicted four-stranded β-sheet core, five α-helices, and two acidic loops. Association of Gadd45β with MKK7 involves a network of interactions mediated by its putative helices α3 and α4 and loops 1 and 2. Whereas α3 appears to primarily mediate docking to MKK7, loop 1 and α4-loop 2 seemingly afford kinase inactivation by engaging the ATP-binding site and causing conformational changes that impede catalytic function. These data provide a basis for Gadd45β-mediated blockade of MKK7, and ultimately, TNFα-induced PCD. They also have important implications for treatment of widespread diseases. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.}, keywords={Cell Death, Conformations, Enzyme Inhibition, Molecular Interactions, Molecular Structure, Tumors, Kinase, Structured Proteins, Tumor Necrosis Factor (tnf), Enzyme Activity, Adenosine Triphosphate, Growth Arrest And Dna Damage Inducible Protein 45, Mitogen Activated Protein Kinase Kinase 7, Mitogen Activated Protein Kinase P38, Stress Activated Protein Kinase, Tumor Necrosis Factor Alpha, Alpha Helix, Apoptosis, Article, Beta Chain, Catalysis, Enzyme Inactivation, Enzyme Structure, Priority Journal, Protein Conformation, Protein Function, Protein Interaction, Amino Acid Sequence, Antigens, Differentiation, Enzyme Activation, Humans, Map Kinase Kinase 7, Molecular Sequence Data, Nf-Kappa B, Protein Structure, Secondary, Tertiary, Signal Transduction, Structure-Activity Relationship, Tumor Necrosis Factor-Alpha, }, references={Kucharczak, J., Simmons, M.J., Fan, Y., Gelinas, C., (2003) Oncogene, 22, pp. 8961-898 Papa, S., Bubici, C., Zazzeroni, F., Pham, C.G., Kuntzen, C., Knabb, J.R., Dean, K., Franzoso, G., (2006) Cell Death Differ, 13, pp. 712-729 Karin, M., (2006) Nature, 441, pp. 431-436 Claudio, E., Brown, K., Siebenlist, U., (2006) Cell Death Differ, 13, pp. 697-701 Kim, H.J., Hawke, N., Baldwin, A.S., (2006) Cell Death Differ, 13, pp. 738-747 De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D.U., Jin, R., Jones, J., Cong, R., Franzoso, G., (2001) Nature, 414, pp. 308-313 Tang, G., Minemoto, Y., Dibling, B., Purcell, N.H., Li, Z., Karin, M., Lin, A., (2001) Nature, 414, pp. 313-317 Davis, R.J., (2000) Cell, 103, pp. 239-252 Deng, Y., Ren, X., Yang, L., Lin, Y., Wu, X., (2003) Cell, 115, pp. 61-70 Chang, L., Kamata, H., Solinas, G., Luo, J.L., Maeda, S., Venuprasad, K., Liu, Y.C., Karin, M., (2006) Cell, 124, pp. 601-613 Papa, S., Zazzeroni, F., Bubici, C., Jayawardena, S., Alvarez, K., Matsuda, S., Nguyen, D.U., Franzoso, G., (2004) Nat. 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Biol. Chem, 275, pp. 16602-16608 Bulavin, D.V., Kovalsky, O., Hollander, M.C., Fornace Jr., A.J., (2003) Mol. Cell. Biol, 23, pp. 3859-3871 Salvador, J.M., Mittelstadt, P.R., Belova, G.I., Fornace Jr., A.J., Ashwell, J.D., (2005) Nat. Immunol, 6, pp. 396-402 Kim, H. J., Hawke, N., Baldwin, A. S., (2006) Cell Death Differ, 13, pp. 738-747 Davis, R. J., (2000) Cell, 103, pp. 239-252 Liebermann, D. A., Hoffmann, B., (2002) Oncogene, 21, pp. 3391-3402 Snyder, E. L., Dowdy, S. F., (2001) Curr. Opin Mol. Ther, 3, pp. 147-152 Yang, J. T., Wu, C. S., Martinez, H. M., (1986) Methods Enzymol, 130, pp. 208-269 Koonin, E. V., (1997) J. Mol. Med, 75, pp. 236-238 Hubbard, S. R., (1997) EMBO J, 16, pp. 5572-5581 Ohren, J. F., Chen, H., Pavlovsky, A., Whitehead, C., Zhang, E., Kuffa, P., Yan, C., Hasemann, C. A., (2004) Nat. Struct. Mol. Biol, 11, pp. 1192-1197 Russo, A. A., Jeffrey, P. D., Patten, A. K., Massague, J., Pavletich, N. P., (1996) Nature, 382, pp. 325-331 Bulavin, D. V., Kovalsky, O., Hollander, M. C., Fornace Jr., A. J., (2003) Mol. Cell. Biol, 23, pp. 3859-3871 Salvador, J. M., Mittelstadt, P. R., Belova, G. I., Fornace Jr., A. J., Ashwell, J. D., (2005) Nat. Immunol, 6, pp. 396-402}, document_type={Journal Article, Research Support, N. I. H. , Extramural, Non-U. S. Gov'T, }, affiliation={Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, United States Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale Delle Ricerche, Via Mezzocannone 16, 80134 Napoli, Italy Dept. of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy The Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.}, ibbaffiliation={1}, } @article{IBB_ID_52879, author={Hangen E, Féraud O, Lachkar S, Mou H, Doti N, Fimia GM, Lam N-V, Zhu C, Godin I, Muller K, Chatzi A, Nuebel E, Ciccosanti F, Flamant S, Bénit P, Perfettini J-L, Sauvat A, Bennaceur-Griscelli A, Ser-Le Roux K, Gonin P, Tokatlidis K, Rustin P, Piacentini M, Ruvo M, Blomgren K, Kroemer G, Modjtahedi N}, title={Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis}, date={2015}, journal={Mol Cell (ISSN: 1097-2765, 1097-4164)}, year={2015}, fullvolume={456}, volume={456}, pages={1001--1014}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84937630298&partnerID=40&md5=a3419da71197a64904a4486caa54de4e}, abstract={Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, beyond its apoptotic function, is required for the normal expression of major respiratory chain complexes. Here we identified an AIF-interacting protein, CHCHD4, which is the central component of a redox-sensitive mitochondrial intermembrane space import machinery. Depletion or hypomorphic mutation of AIF caused a downregulation of CHCHD4 protein by diminishing its mitochondrial import. CHCHD4 depletion sufficed to induce a respiratory defect that mimicked that observed in AIF-deficient cells. CHCHD4 levels could be restored in AIF-deficient cells by enforcing its AIF-independent mitochondrial localization. This modified CHCHD4 protein reestablished respiratory function in AIF-deficient cells and enabled AIF-deficient embryoid bodies to undergo cavitation, a process of programmed cell death required for embryonic morphogenesis. These findings explain how AIF contributes to the biogenesis of respiratory chain complexes, and they establish an unexpected link between the vital function of AIF and the propensity of cells to undergo apoptosis. © 2015 Elsevier Inc.}, keywords={Small Interfering Rna, Thiol Oxidase, Apoptosis, Article, Biogenesis, Breathing, Cell Death, Deletion Mutant, Depletion, Embryo Development, Escherichia Coli, Image Analysis, Immunoprecipitation, Inner Membrane, Isothermal Titration Calorimetry, Membrane Potential, Mitochondrial Targeting Signal, Morphogenesis, Phenotype, Protein Expression, Protein Protein Interaction, Respiratory Chain, Respiratory Function, Stable Transfection, }, references={Allen, S., Balabanidou, V., Sideris, D.P., Lisowsky, T., Tokatlidis, K., Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c (2005) J. Mol. 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Biol., 9, pp. 680-684}, document_type={Journal Article, }, affiliation={Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France INSERM, UMRS 1138, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France Université Pierre et Marie Curie, Paris, France Université Paris Sud/Paris XI, Kremlin Bicêtre, France INSERM U935, Villejuif, France ESTeam Paris Sud, Stem Cell Core Facility, Institut André Lwoff, Villejuif, France Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases IRCCS L. Spallanzani, Rome, Italy Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden INSERM U1009, Villejuif, France Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom INSERM UMR1141, Hôpital Robert Debré, Paris, France Faculté de Médecine Denis Diderot, Université Paris 7, Paris, France Cell Death and Aging Team, Gustave Roussy, Villejuif, France INSERM U1030, Gustave Roussy, Villejuif, France Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France Laboratoire d'Hématologie, Hôpital Paul Brousse AP-HP, Villejuif, France Animal and Veterinary Resources, Villejuif, France Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France 1Equipe 11 labellise´ e par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, Fra}, ibbaffiliation={1}, } @article{IBB_ID_54801, author={Cimmino I, Prisco F, Orso S, Agognon AL, Liguoro P, De Biase D, Doti N, Ruvo M, Paciello O, Beguinot F, Formisano P, Oriente F}, title={Interleukin 6 reduces vascular smooth muscle cell apoptosis via Prep1 and is associated with aging}, date={2021 Nov}, journal={Faseb J (ISSN: 0892-6638linking)}, year={2021}, fullvolume={5}, volume={5}, pages={e21989--N/D}, url={}, abstract={Aging exacerbates neointimal formation by reducing apoptosis of vascular smooth muscle cells (VSMCs) and induces inflammation within vascular wall. Prep1 is a homeodomain transcription factor which stimulates the expression of proinflammatory cytokines in aortic endothelial cell models and plays a primary role in the regulation of apoptosis. In this study, we have investigated the role of Prep1 in aorta of Prep1 hypomorphic heterozygous mice (Prep1(i/+) ) and in VSMCs, and its correlation with aging. Histological analysis from Prep1(i/+) aortas revealed a 25% reduction in medial smooth muscle cell density compared to WT animals. This result paralleled higher apoptosis, caspase 3, caspase 9 and p53 levels in Prep1(i/+) mice and lower Bcl-xL. Prep1 overexpression in VSMCs decreased apoptosis by 25% and caspase 3 and caspase 9 expression by 40% and 37%. In parallel, Bcl-xL inhibition by BH3I-1 and p53 induction by etoposide reverted the antiapoptotic effect of Prep1. Experiments performed in aorta from 18 months old WT mice showed a significant increase in Prep1, p16(INK4) , p21(Waf1) and interleukin 6 (IL-6) compared to youngest animals. Similar results have been observed in H(2) O(2) -induced senescent VSMCs. Interestingly, the synthetic Prep1 inhibitory peptide Prep1 (54-72) reduced the antiapoptotic effects mediated by IL-6, particularly in senescent VSMCs. These results indicate that IL-6-Prep1 signaling reduces apoptosis, by modulating Bcl-xL and p53 both in murine aorta and in VSMCs. In addition, age-dependent increase in IL-6 and Prep1 in senescent VSMCs and in old mice may be involved in the aging-related vascular dysfunction.}, keywords={Prep1, Aging, Apoptosis, Interleukin 6, Vascular Smooth Muscle Cells}, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T}, affiliation={Department of Translational Medicine, Federico II University of Naples and URT "Genomic of Diabetes" of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy. Department of Veterinary Medicine and Animal Production, Federico II University of Naples, Naples, Italy. Institute of Biostructure and Bioimaging, National Research Council and Interuniversity Research Centre on Bioactive Peptides Naples, Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53859, author={Balasco N, Barone D, Iaccarino E, Sandomenico A, De Simone A, Ruvo M, Vitagliano L}, title={Intrinsic structural versatility of the highly conserved 412-423 epitope of the Hepatitis C Virus E2 protein}, date={2018 Sep}, journal={Int J Biol Macromol (ISSN: 1879-0003electronic, 0141-8130linking)}, year={2018}, fullvolume={246}, volume={246}, pages={620--632}, url={}, abstract={HCV infection is a major threaten for human health as it affects hundreds of million people worldwide. Here we investigated the conformational properties of the 412-423 fragment of the envelope E2 protein, one of the most immunogenic regions of the virus proteome whose characterization may provide interesting insights for anti-HCV vaccine development. The spectroscopic characterization of the polypeptide unravels its unexpected tendency to form amyloid-like aggregates. When kept in monomeric state, it shows a limited tendency to adopt regular secondary structure. Enhanced molecular dynamics simulations, starting from four distinct conformational states, highlight its structural versatility. Interestingly, all multiform conformational states of the polypeptide detected in crystallographic complexes with antibodies are present in the structural ensemble of all simulations. This observation corroborates the idea that known antibodies recognize this region through a conformational selection mechanism. Accordingly, the design of effective anti-HCV vaccines should consider the intrinsic flexibility of this region. The structural versatility of the 412-423 region is particularly puzzling if its remarkable sequence conservation is considered. It is likely that flexibility and sequence conservation are important features that endow this epitope with the ability to accomplish distinct functions such as immunity escape and interaction with host receptors.}, keywords={Amyloid-Like Aggregates, Pathogen-Host Recognition, Protein Flexibility, Replica Exchange Molecular Dynamics, Epitopes Chemistry , Hepacivirus Chemistry , Molecular Dynamics Simulation , Viral Hepatitis Vaccines Chemistry , Viral Proteins Chemistry, }, references={}, document_type={Journal Article, }, affiliation={Institute of Biostructures and Bioimaging, CNR, Naples I-80134, Italy. Electronic address: nicole.balasco@unicampania.it., Institute of Biostructures and Bioimaging, CNR, Naples I-80134, Italy; Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Universita della Campania "Luigi Vanvitelli", Caserta 81100, Italy., Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, UK., Institute of Biostructures and Bioimaging, CNR, Naples I-80134, Italy. Electronic address: luigi.vitagliano@unina.it., }, ibbaffiliation={1}, } @article{IBB_ID_9312, author={Chambery A, Pisante M, Di Maro A, Di Zazzo E, Ruvo M, Costantini S, Colonna G, Parente A}, title={Invariant Ser211 is involved in the catalysis of PD-L4, type I RIP from Phytolacca dioica leaves}, date={2007 Apr 1}, journal={Proteins (ISSN: 0887-3585, 1097-0134, 1097-0134electronic)}, year={2007}, fullvolume={337}, volume={337}, pages={209--218}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33847399669&partnerID=40&md5=488bd05d9de230aaac9d56c1395edf1d}, abstract={Multiple sequence alignment analysis of ribosome inactivating proteins (RIPs) has revealed the occurrence of an invariant seryl residue in proximity of the catalytic tryptophan. The involvement of this seryl residue in the catalytic mechanism of RIPs was investigated by site-directed mutagenesis in PD-L4, type 1 RIP isolated from Phytolacca dioica leaves. We show that the replacement of Ser211 with Ala apparently does not influence the N-β-glycosidase activity on ribosomes (determined as IC50 in a cell-free system), but it reduces the adenine polynucleotide glycosylase activity (APG), assayed spectrophotometrically on other substrates such as DNA, rRNA, and poly(A). The ability of PDL4 to deadenylate polynucleotides appears more sensitive to the Ser211Ala replacement when poly(A) is used as substrate, as only 33% activity is retained by the mutant, while with more complex and heterogeneous substrates such as DNA and rRNA, its APG activity is 73% and 66%, respectively. While the mutated protein shows a conserved secondary structure by CD, it also exhibits a remarkably enhanced tryptophan fluorescence. This indicates that, although the overall protein tridimensional structure is maintained, removal of the hydrosyl group locally affects the environment of a Trp residue. Modelling and docking analyses confirm the interaction between Ser211 and Trp207, which is located within the active site, thus affecting RIP adenine polynucleotide glycosylase activity. Data accumulated so far confirm the potential involvement of Ser211 in the catalytic mechanism of type 1 RIP PD-L4 and a possible role in stabilizing the conformation of Trp207 side chain, which participates actively in the protein enzymatic activity. © 2007 Wiley-Liss, Inc.}, keywords={3d Modelling, Adenine Polynucleotide Glycosylases, Circular Dichroic Spectroscopy, Docking Analysis, Fluorescence Analyses, Ribosome Inactivating Proteins, Complementary Dna, Dna Glycosyltransferase, Polyadenylic Acid, Ribosome Rna, Serine, Unclassified Drug, Article, Catalysis, Enzyme Activity, Enzyme Substrate, Fluorescence Spectroscopy, Molecular Model, Nonhuman, Plant Leaf, Pokeweed, Priority Journal, Protein Purification, Three Dimensional Imaging, Amino Acid Sequence, Animals, Cell-Free System, Cloning, Computer Simulation, Escherichia Coli, Molecular Sequence Data, Mutagenesis, Site-Directed, N-Glycosyl Hydrolases, Phytolacca, Plant Leaves, Plant Proteins, Rabbits, Reticulocytes, Sequence Alignment, Spectrometry, Phytolacca Dioica, }, references={Barbieri, L., Battelli, M.G., Stirpe, F., Ribosome-inactivating proteins from plants (1993) Biochim Biophys Acta, 1154, pp. 237-28 Barbieri, L., Valbonesi, P., Bonora, E., Gorini, P., Bolognesi, A., Stirpe, F., Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins: Effect on DNA, RNA and poly(A) (1997) Nucleic Acids Res, 25, pp. 518-522 Bolognesi, A., Polito, L., Lubelli, C., Barbieri, L., Parente, A., Stirpe, F., Ribosome-inactivating and adenine polynucleotide glycosylase activities in Mirabilis jalapa L. tissues (2002) J Biol Chem, 277, pp. 13709-13716 Wang, P., Tumer, N.E., Virus resistance mediated by ribosome inactivating proteins (2000) Adv Virus Res, 55, pp. 325-355 Nielsen, K., Boston, R.S., Ribosome-inactivating proteins: A plant perspective (2001) Annu Rev Plant Physiol Plant Mol Biol, 52, pp. 785-816 Parikh, B.A., Tumer, N.E., Antiviral activity of ribosome inactivating proteins in medicine (2004) Mini Rev Med Chem, 4, pp. 523-543 Hong, Y., Saunders, K., Hartley, M.R., Stanley, J., Resistance to geminivirus infection by virus-induced expression of dianthin in transgenic plants (1996) Virology, 220, pp. 119-127 Lodge, J.K., Kaniewski, W.K., Tumer, N.E., Broad-spectrum virus resistance in transgenic plants expressing pokeweed antiviral protein (1993) Proc Natl Acad Sci USA, 90, pp. 7089-7093 Corrado, G., Delli Bovi, P., Ciliento, R., Gaudio, L., Di Maro, A., Aceto, S., Lorito, M., Rao, R., Inducible expression of a Phytolacca heterotepala ribosome-inactivating protein leads to enhanced resistance against major fungal pathogens in tobacco (2005) Phytopathology, 95, pp. 206-215 Ready, M.P., Kim, Y., Robertus, J.D., Site-directed mutagenesis of ricin A-chain and implications for the mechanism of action (1991) Proteins, 10, pp. 270-278 Katzin, B.J., Collins, E.J., Robertus, J.D., Structure of ricin A-chain at 2.5 A (1991) Proteins, 10, pp. 251-259 Gawlak, S.L., Neubauer, M., Klei, H.E., Chang, C.Y., Einspahr, H.M., Siegall, C.B., Molecular, biological, and preliminary structural analysis of recombinant bryodin 1, a ribosome-inactivating protein from the plant Bryonia dioica (1997) Biochemistry, 36, pp. 3095-3103 Schlossman, D., Withers, D., Welsh, P., Alexander, A., Robertus, J., Frankel, A., Role of glutamic acid 177 of the ricin toxin A chain in enzymatic inactivation of ribosomes (1989) Mol Cell Biol, 9, pp. 5012-5021 Frankel, A., Welsh, P., Richardson, J., Robertus, J.D., Role of arginine 180 and glutamic acid 177 of ricin toxin A chain in enzymatic inactivation of ribosomes (1990) Mol Cell Biol, 10, pp. 6257-6263 Gould, J.H., Hartley, M.R., Welsh, P.C., Hoshizaki, D.K., Frankel, A., Roberts, L.M., Lord, J.M., Alteration of an amino acid residue outside the active site of the ricin A chain reduces its toxicity towards yeast ribosomes (1991) Mol Gen Genet, 230, pp. 81-90 Mlsna, D., Monzingo, A.F., Katzin, B.J., Ernst, S., Robertus, J.D., Structure of recombinant ricin A chain at 2.3 A (1993) Protein Sci, 2, pp. 429-435 Funatsu, G., Islam, M.R., Minami, Y., Sung-Sil, K., Kimura, M., Conserved amino acid residues in ribosome-inactivating proteins from plants (1991) Biochimie, 73, pp. 1157-1161 Di Maro, A., Valbonesi, P., Bolognesi, A., Stirpe, F., De Luca, P., Siniscalco Gigliano, G., Gaudio, L., Parente, A., Isolation and characterization of four type-1 ribosome-inactivating proteins, with polynucleotide:adenosine glycosidase activity, from leaves of Phytolacca dioica L (1999) Planta, 208, pp. 123-131 Sambrook, J., Fritsch, E., Maniatis, T., (1989) Molecular cloning: A laboratory manual, , 2nd ed. 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J., Gapped BLAST and PSI-BLAST: A new generation of protein database search programs (1997) Nucleic Acids Res, 25, pp. 3389-3402 Facchiano, A. M., Stiuso, P., Chiusano, M. L., Caraglia, M., Giuberti, G., Marra, M., Abbruzzese, A., Colonna, G., Homology modelling of the human eukaryotic initiation factor 5A (eIF-5A) (2001) Protein Eng, 14, pp. 881-890 Sippl, M. J., Recognition of errors in three-dimensional structures of proteins (1993) Proteins, 17, pp. 355-362 Canutescu, A. A., Shelenkov, A. A., Dunbrack Jr, R. L., A graph-theory algorithm for rapid protein side-chain prediction (2003) Protein Sci, 12, pp. 2001-2014 Dunbrack Jr., R. L., Rotamer libraries in the 21st century (2002) Curr Opin Struct Biol, 12, pp. 431-440 Orengo, C. A., Michie, A. D., Jones, S., Jones, D. T., Swindells, M. B., Thornton, J. M., CATH-a hierarchic classification of protein domain structures (1997) Structure, 5, pp. 1093-1108 McDonald, I. K., Thornton, J. M., Satisfying hydrogen bonding potential in proteins (1994) J Mol Biol, 238, pp. 777-793 Wang, Y. X., Neamati, N., Jacob, J., Palmer, I., Stahl, S. J., Kaufman, J. D., Huang, P. L., Torchia, D. A., Solution structure of anti-HIV-1 and anti-tumor protein MAP30: Structural insights into its multiple functions (1999) Cell, 99, pp. 433-442 Wang, Y. X., Jacob, J., Wingfield, P. T., Palmer, I., Stahl, S. J., Kaufman, J. D., Huang, P. L., Torchia, D. A., Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP (2000) Protein Sci, 9, pp. 138-144 Facchiano, A. M., Colonna, G., Ragone, R., Helix stabilizing factors and stabilization of thermophilic proteins: An X-ray based study (1998) Protein Eng, 11, pp. 753-760 Kurinov, I. V., Myers, D. E., Irvin, J. D., Uckun, F. M., X-ray crystallographic analysis of the structural basis for the interactions of pokeweed antiviral protein with its active site inhibitor and ribosomal RNA substrate analogs (1999) Protein Sci, 8, pp. 1765-1772 Marsden, C. J., Fulop, V., Day, P. J., Lord, J. M., The effect of mutations surrounding and within the active site on the catalytic activity of ricin A chain (2004) Eur J Biochem, 271, pp. 153-162 Robertus, J. D., Monzingo, A. F., The structure of ribosome inactivating proteins (2004) Mini Rev Med Chem, 4, pp. 477-486 Chen, J. K., Hung, C. H., Liaw, Y. C., Lin, J. Y., Identification of amino acid residues of abrin-a A chain is essential for catalysis and reassociation with abrin-a B chain by site-directed mutagenesis (1997) Protein Eng, 10, pp. 827-833 Fryxell, D. K., Gawlak, S. L., Dodge, R. W., Siegall, C. B., Identification of a specific tyrosine residue in Bryodin 1 distinct from the active site but required for full catalytic and cytotoxic activity (1998) Protein Sci, 7, pp. 318-324}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze della Vita, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, I-80138 Napoli, Italy Dipartimento di Biochimica e Biofisica, CRISCEB (Centro di Ricerca Interdipartimentale per le Scienze Computazionali e Biotecnologiche), Seconda Università di Napoli, Via Costantinopoli 16, I-80138 Napoli, Italy Istituto di Scienze dell'Alimentazione, CNR, Via Roma 52 A/C, 83100 Avellino, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54237, author={Iaccarino E, Sandomenico A, Corvino G, Foca G, Severino V, Russo R, Caporale A, Raimondo D, D'Abramo M, Alba J, Chambery A, Ruvo M}, title={Investigating the oxidative refolding mechanism of Cripto-1 CFC domain}, date={2019 Sep 15}, journal={Int J Biol Macromol (ISSN: 0141-8130linking, 1879-0003electronic)}, year={2019}, fullvolume={281}, volume={281}, pages={1179--1189}, url={}, abstract={Using a combined approach based on MS, enzyme digestion and advanced MD studies we have determined the sequential order of formation of the three disulfide bridges of the Cripto-1 CFC domain. The domain has a rare pattern of bridges and is involved in the recognition of several receptors. The bridge formation order is C1-C4, C3-C5, C2-C6, however formation of C1-C4 plays no roles for the formation of the others. Folding is driven by formation of the C3-C5 bridge and is supported by residues lying within the segment delimited by these cysteines. We indeed observe that variants CFC-W123A and CFC-DeltaC1/C4, where C1 and C4 are replaced by serines, are able to refold in the same time window as the wild type, while CFC-K132A and CFC-W134A are not. A variant where cysteines of the second and third bridge are mutated to serine, convert slowly to the monocyclic molecule. Data altogether support a mechanism whereby the Cripto-1 CFC domain refolds by virtue of long-range intramolecular interactions that involve residues close to cysteines of the second and third bridge. These findings are supported by the in silico study that shows how distant parts of the molecules come into contact on a long time scale.}, keywords={Cfc Domain, Cripto, Disulfide Bridges, Oxidative Folding, Amino Acid Sequence , Disulfides Chemistry , Gpi-Linked Proteins Chemistry Metabolism , Humans , Intercellular Signaling Peptides And Proteins Chemistry Metabolism , Kinetics , Molecular Dynamics Simulation , Neoplasm Proteins Chemistry Metabolism , Oxidation-Reduction , Peptide Fragments Chemistry , Protein Domains , Protein Refolding, }, references={}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche (DISTABIF), via Vivaldi, 43, 80100 Caserta, Italy Istituto di Biostrutture e Bioimmagini, CNR and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Napoli, Italy. Dipartimento di Medicina Molecolare, Sapienza Universita di Roma, 00161, Italy. Dipartimento di Chimica, Sapienza Universita di Roma, 00161, Italy. Anbition srl, via A. Manzoni, 1, 80123 Napoli, Italy. Electronic address: menotti.ruvo@unina.it.}, ibbaffiliation={1}, } @article{IBB_ID_54093, author={Giaquinto M, Micco A, Aliberti A, Ricciardi A, Ruvo M, Cutolo A, Cusano A}, title={Lab on fiber biosensors integrated with microgels}, date={2014}, journal={Opt Infobase Conf Pap (ISSN: 9780-960038053)}, year={2014}, fullvolume={210}, volume={210}, pages={N/D--N/D}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019521739&doi=10.1364%2fAPOS.2016.W1A.4&partnerID=40&md5=ad4f7d4d65865b4b67ab36cc576e0a47}, abstract={We experimentally demonstrate a novel optical fiber label free biosensing platform resulting from the integration between Lab-on-Fiber Technology and Microgels Photonics. The novel platform allows to overcome the main issues associated to small molecule detection. © OSA 2016.}, keywords={Optical Fibers, Optical Sensors, Fiber Biosensors, Fiber Technology, Label-Free Biosensing, Micro-Gels, Small Molecule Detections, }, references={Ricciardi, A., (2015) Analyst, 140, pp. 8068-807 Cusano, A., (2014) Lab-on-Fiber Technology, , ed. (Springer Series in Surface Sciences) Manikas, A., (2015) J. Mater. Chem. B, 3, pp. 53-58 Guan, Y., (2013) Chem. Soc. Rev, 42, pp. 8106-8121 Sorrell, C.D., (2012) Anal BioanalChem, 402, pp. 2385-2393 Toma, M., (2013) Phys. Chem. C, 117, pp. 11705-11712 Mesch, M., (2015) ACS Photonics, 2, pp. 475-480}, document_type={Conference, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, I-82100, Italy Institute of Biostructure and Bioimaging, National Research Council, Napoli, I-80143, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53842, author={Giaquinto M, Ricciardi A, Aliberti A, Micco A, Bobeico E, Ruvo M, Cusano A}, title={Light-microgel interaction in resonant nanostructures}, date={2018 Jun 19}, journal={Sci Rep (ISSN: 2045-2322linking, 2045-2322electronic)}, year={2018}, fullvolume={318}, volume={318}, pages={9331--9331}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045122478&doi=10.1038%2fs41598-018-27197-4&partnerID=40&md5=fae23c5a7ca1c65a5b938c2c8df043b4}, abstract={Combination of responsive microgels and photonic resonant nanostructures represents an intriguing technological tool for realizing tunable and reconfigurable platforms, especially useful for biochemical sensing applications. Interaction of light with microgel particles during their swelling/shrinking dynamics is not trivial because of the inverse relationships between their size and refractive index. In this work, we propose a reliable analytical model describing the optical properties of closed-packed assembly of surface-attached microgels, as a function of the external stimulus applied. The relationships between the refractive index and thickness of the equivalent microgel slab are derived from experimental observations based on conventional morphological analysis. The model is first validated in the case of temperature responsive microgels integrated on a plasmonic lab-on-fiber optrode, and also implemented in the same case study for an optical responsivity optimization problem. Overall, our model can be extended to other photonic platforms and different kind of microgels, independently from the nature of the stimulus inducing their swelling. © 2018 The Author(s).}, keywords={, }, references={Pelton, R., Hoare, T., Microgels and their synthesis: An introduction (2011) Microgel Suspensions: Fundamentals and Applications, 1, pp. 1-3 Hendrickson, G.R., Smith, M.H., South, A.B., Lyon, L.A., Design of multiresponsive hydrogel particles and assemblies (2010) Advanced Functional Materials, 20, pp. 1697-1712 Hoare, T., Pelton, R., Highly pH and temperature responsive microgels functionalized with vinylacetic acid (2004) Macromolecules, 37, pp. 2544-2550 Debord, J.D., Lyon, L.A., Synthesis and characterization of pH-responsive copolymer microgels with tunable volume phase transition temperatures (2003) Langmuir, 19, pp. 7662-7664 Jochum, F.D., Theato, P., Temperature- A nd light-responsive smart polymer materials (2013) Chem Soc Rev, 42, pp. 7468-7483 Plamper, F.A., Richtering, W., Functional Microgels and Microgel Systems (2017) Accounts Chem Res, 50, pp. 131-140 Buenger, D., Topuz, F., Groll, J., Hydrogels in sensing applications (2012) Prog Polym Sci, 37, pp. 1678-1719 Wei, M.L., Gao, Y.F., Li, X., Serpe, M.J., Stimuli-responsive polymers and their applications (2017) Polym Chem-UK, 8, pp. 127-143 Sorrell, C.D., Serpe, M.J., Glucose sensitive poly (N-isopropylacrylamide) microgel based etalons (2012) Anal Bioanal Chem, 402, pp. 2385-2393 Islam, M.R., Serpe, M.J., Polyelectrolyte mediated intra and intermolecular crosslinking in microgel-based etalons for sensing protein concentration in solution (2013) Chem Commun, 49, pp. 2646-2648 Islam, M.R., Ahiabu, A., Li, X., Serpe, M.J., Poly (N-isopropylacrylamide) microgel-based optical devices for sensing and biosensing (2014) Sensors-Basel, 14, pp. 8984-8995 Tsuji, S., Kawaguchi, H., Colored thin films prepared from hydrogel microspheres (2005) Langmuir, 21, pp. 8439-8442 Nerapusri, V., Keddie, J.L., Vincent, B., Bushnak, I.A., Swelling and deswelling of adsorbed microgel monolayers triggered by changes in temperature, pH, and electrolyte concentration (2006) Langmuir, 22, pp. 5036-5041 Serpe, M.J., Jones, C.D., Lyon, L.A., Layer-by-layer deposition of thermoresponsive microgel thin films (2003) Langmuir, 19, pp. 8759-8764 South, A.B., Whitmire, R.E., Garcia, A.J., Lyon, L.A., Centrifugal deposition of microgels for the rapid assembly of nonfoulingthin films (2009) Acs Appl Mater Inter, 1, pp. 2747-2754 Sorrell, C.D., Carter, M.C.D., Serpe, M.J., Color tunable poly (n-isopropylacrylamide)-co-acrylic acid microgel-au hybrid assemblies (2011) Advanced Functional Materials, 21, pp. 425-433 Giaquinto, M., Microgel photonics and lab on fiber technology for advanced label free fiber optic nanoprobes (2016) Proc Spie, p. 9916 Aliberti, A., Microgel assisted lab-on-fiber optrode (2017) Sci Rep-UK, p. 7 Ricciardi, A., Aliberti, A., Giaquinto, M., Micco, A., Cusano, A., Microgel Photonics: A breathing cavity onto optical fiber tip (2015) Proc Spie, p. 9634 Carotenuto, B., Optical guidance systems for epidural space identification (2017) Ieee J Sel Top Quant, p. 23 Pelton, R., Adv. Colloids Interface Sci (2000), 85, pp. 1-33 Aulasevich, A., Optical waveguide spectroscopy for the investigation of protein-functionalized hydrogel films (2009) Macromol Rapid Comm, 30, pp. 872-877 Burmistrova, A., Steitz, R., Von Klitzing, R., Temperature response of pnipam derivatives at planar surfaces: Comparison between polyelectrolyte multilayers and adsorbed microgels (2010) Chemphyschem, 11, pp. 3571-3579 Li, H., (2009) In Smart Hydrogel Modelling, pp. 57-114. , Springer Gupta, D.K., Karthickeyan, D., Tata, B.V.R., Ravindran, T.R., Temperature-driven volume phase transition of a single stimuli-responsive microgel particle using optical tweezers (2016) Colloid Polym Sci, 294, pp. 1901-1908 Howe, A.J., Howe, A.M., Routh, A.F., The viscosity of dilute poly(N-isopropylacrylamide) dispersions (2011) J Colloid Interf Sci, 357, pp. 300-307 Romeo, G., Imperiali, L., Kim, J.W., Fernandez-Nieves, A., Weitz, D.A., Origin of de-swelling and dynamics of dense ionic microgel suspensions (2012) J Chem Phys, 136 Consales, M., Lab-on-fiber technology: Toward multifunctional optical nanoprobes (2012) Acs Nano, 6, pp. 3163-3170. , 22401595 Ricciardi, A., Versatile optical fiber nanoprobes: From plasmonic biosensors to polarization-sensitive devices (2014) Acs Photonics, 1, pp. 69-78 Cusano, A., Consales, M., Crescitelli, A., Ricciardi, A., (2015) Lab-on-fiber Technology, 56. , Springer Ricciardi, A., Lab-on-fiber technology: A new vision for chemical and biological sensing (2015) Analyst, 140, pp. 8068-8079. , 2015Ana.140.8068R 26514109 Vaiano, P., Lab on fiber technology for biological sensing applications (2016) Laser Photonics Rev, 10, pp. 922-961 Ebbesen, T.W., Lezec, H.J., Ghaemi, H.F., Thio, T., Wolff, P.A., Extraordinary optical transmission through sub-wavelength hole arrays (1998) Nature, 391, pp. 667-669. , 1998Natur.391.667E Micco, A., Ricciardi, A., Pisco, M., La Ferrara, V., Cusano, A., Optical fiber tip templating using direct focused ion beam milling (2015) Sci Rep-UK, p. 5 Dahlin, A.B., Wittenberg, N.J., Hoök, F., Oh, S.-H., Promises and challenges of nanoplasmonic devices for refractometric biosensing (2013) Nanophotonics, 2, pp. 83-101 Spackova, B., Wrobel, P., Bockova, M., Homola, J., Optical biosensors based on plasmonic nanostructures: A review (2016) P IEEE, 104, pp. 2380-2408 Giaquinto, M., Ricciardi, A., Cutolo, A., Cusano, A., Lab-on-fiber plasmonic probes for ultrasound detection: A comparative study (2016) J Lightwave Technol, 34, pp. 5189-5198 Zhang, Z.Y., Zhao, P., Lin, P., Sun, F.G., Thermo-optic coefficients of polymers for optical waveguide applications (2006) Polymer, 47, pp. 4893-4896 Kamikawachi, R.C., Determination of thermo-optic coefficient in liquids with fiber Bragg grating refractometer (2008) Opt Commun, 281, pp. 621-625 Horecha, M., Ordered surface structures from PNIPAM-based loosely packed microgel particles (2010) Soft Matter, 6, pp. 5980-5992 Plunkett, K.N., Zhu, X., Moore, J.S., Leckband, D.E., PNIPAM chain collapse depends on the molecular weight and grafting density (2006) Langmuir, 22, pp. 4259-4266 Schmidt, S., Motschmann, H., Hellweg, T., Von Klitzing, R., Thermoresponsive surfaces by spin-coating of PNIPAM-co-PAA microgels: A combined AFM and ellipsometry study (2008) Polymer, 49, pp. 749-756 Wiedemair, J., In-situ AFM studies of the phase-transition behavior of single thermoresponsive hydrogel particles (2007) Langmuir, 23, pp. 130-137 Palik, E.D., (1998) Handbook of Optical Constants of Solids, 3. , Academic press Malitson, I., Interspecimen comparison of the refractive index of fused silica (1965) Josa, 55, pp. 1205-1209}, document_type={Journal Article, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, I-82100, Benevento, Italy. ENEA, Portici Research Center, P.le E. Fermi 1, I-80055 Portici, Napoli, Italy. Institute of Biostructure and Bioimaging, National Research Council, I-80143, Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53151, author={Quero G, Consales M, Severino R, Vaiano P, Boniello A, Sandomenico A, Ruvo M, Borriello A, Diodato L, Zuppolini S, Giordano M, Nettore IC, Mazzarella C, Colao A, Macchia PE, Santorelli F, Cutolo A, Cusano A}, title={Long period fiber grating nano-optrode for cancer biomarker detection}, date={2016 Feb 13}, journal={Biosens Bioelectron (ISSN: 0956-5663, 1873-4235electronic)}, year={2016}, fullvolume={198}, volume={198}, pages={590--600}, url={https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84958279448&partnerID=40&md5=c96f2cbabc0f0d7d7978b2176151767d}, abstract={ We report an innovative fiber optic nano-optrode based on Long Period Gratings (LPGs) working in reflection mode for the detection of human Thyroglobulin (TG), a protein marker of differentiated thyroid cancer. The reflection-type LPG (RT-LPG) biosensor, coated with a single layer of atactic polystyrene (aPS) onto which a specific, high affinity anti-Tg antibody was adsorbed, allowed the label-free detection of Tg in the needle washouts of fine-needle aspiration biopsies, at concentrations useful for pre- and post-operative assessment of the biomarker levels. Analyte recognition and capture were confirmed with a parallel on fiber ELISA-like assay using, in pilot tests, the biotinylated protein and HRP-labeled streptavidin for its detection. Dose-dependent experiments showed that the detection is linearly dependent on concentration within the range between 0 and 4 ng/mL, while antibody saturation occurs for higher protein levels. The system is characterized by a very high sensitivity and specificity allowing the  ex-vivo  detection of sub ng/ml concentrations of human Tg from needle washouts of fine-needle aspiration biopsies of thyroid nodule from different patients. }, keywords={Biomolecular Sensing, Human Thyroglobulin (tg) Detection, Label-Free Detection, Long Period Fiber Grating (lpg), Optical Fiber Biosensor, Reflection-Type Lpg, Antibodies, Bioassay, Biomarkers, Biopsy, Diffraction Gratings, Fiber Optic Sensors, Glycoproteins, Needles, Reflection Type, Chemical Detection, }, references={Albuja-Cruz, M.B., Thorson, C.M., Allan, B.J., Lew, J.I., Rodgers, (2012) Surgery, 152, pp. 1177-118 Alwis, L., Sun, T., Grattan, K.T.V., (2013) Sens. Actuators B, 178, pp. 694-699 Baldini, F., Brenci, M., Chiavaioli, F., Giannetti, A., Trono, C., (2012) Anal. Bioanal. Chem., 402, pp. 109-116 Brzozowska, E., Śmietana, M., Koba, M., Górska, S., Pawlik, K., Gamian, A., Bock, W.J., (2015) Biosens. 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SPIE 9157, 23rd International Conference on Optical Fibre Sensors Cunha, N., Rodrigues, F., Curado, F., Ilheu, O., Cruz, C., Naidenov, P., Rascao, M., Valido, F., (2007) Eur. J. Endocrinol., 157, pp. 101-107 Cusano, A., Iadicicco, A., Pilla, P., Contessa, L., Campopiano, S., Cutolo, A., Giordano, M., (2006) Opt. Express, 14, pp. 19-34 Dantham, V.R., Holler, S., Barbre, C., Keng, D., Kolchenko, V., Arnold, S., (2013) Nano Lett., 13, pp. 3347-3351 Del Villar, I., Matías, I.R., Arregui, F.J., Lalanne, P., (2005) Opt. Express, 13, pp. 56-69 DeLisa, M.P., Zhang, Z., Shiloach, M., Pilevar, S., Davis, C.C., Sirkis, J.S., Bentley, W.E., (2000) Anal. Chem., 72, pp. 2895-2900 Eftimov, T., Applications of fiber gratings in chemical and biochemical sensing (2010) Optical Guided-Wave Chemical and Biosensors II, Springer Series on Chemical Sensors and Biosensors, 8, pp. 151-176. , Springer, Berlin, Heidelberg, M. Zourob, A. Lakhtakia (Eds.) Endo, T., Kobayashi, T., (2011) Biochem. Biophys. Res. 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Chem., 12, pp. 522-527 Zhang, Y., Shibru, H., Cooper, K.L., Wang, A., (2005) Opt. Lett., 30, pp. 1021-1023}, document_type={Journal Article, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, Italy., Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (IBB-CNR), Napoli, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Napoli, Italy., Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (IBB-CNR), Napoli, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Napoli, Italy. Electronic address: menotti.ruvo@unina.it., Institute for Polymers, Composites and Biomaterials (IPCB) -CNR, Portici, Italy. Electronic address: anna.borriello@cnr.it., Department of Clinical Medicine and Surgery, University of Napoli "Federico II", Napoli, Italy., Department of Traslational Medicine, University of Napoli "Federico II", Napoli, Italy., Hospital Consulting SpA, Bagno a Ripoli, Firenze, Italy., Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, Italy. Electronic address: a.cusano@unisannio.it., }, ibbaffiliation={1}, } @article{IBB_ID_53610, author={Palmieri G, Cocca E, Gogliettino M, Valentino R, Ruvo M, Cristofano G, Angiolillo A, Balestrieri M, Rossi M, Di Costanzo A}, title={Low Erythrocyte Levels of Proteasome and Acyl-Peptide Hydrolase (APEH) Activities in Alzheimer's Disease: A Sign of Defective Proteostasis?}, date={2017}, journal={J Alzheimers Dis (ISSN: 1387-2877, 1387-2877linking)}, year={2017}, fullvolume={323}, volume={323}, pages={1097--1106}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031779417&doi=10.3233%2fJAD-170389&partnerID=40&md5=607c9327d4eee76e9ce54e850679547b}, abstract={Alzheimer's disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia. To date, there are no definitive diagnostic tests that can predict or assess onset and progression of the disease. Blood biomarkers for AD are being sought for many years but their identification remains a challenging task. In this study, we investigated the potential relationship between AD and levels of acyl-peptide hydrolase (APEH) and proteasome in erythrocyte samples of 52 participants (26 AD and 26 cognitively healthy controls). A statistically significant decrease in proteasome and exopeptidase/endopeptidase APEH activities was found in AD samples compared to those of healthy controls. Moreover, in contrast to what was observed for proteasome transcripts, APEH activities reduction in AD patients was unrelated to its gene expression levels, suggesting the occurrence of posttranslational modifications or the expression of endogenous inhibitors that might impair enzyme activity. These preliminary data further support a relationship between the APEH-proteasome system and AD molecular players, providing the first evidence of its potential use as a novel blood-based indicator for the routine detection of AD.}, keywords={Apeh, Alzheimer, S Disease, Blood-Based Indicator System, Oxidized Peptide Hydrolase Activity, Proteasome, Protein Quality Control, Aged , Alzheimer Disease Blood Enzymology , Blotting, Western , Erythrocytes Enzymology , Female , Humans , Peptide Hydrolases Metabolism , Proteasome Endopeptidase Complex Metabolism , Proteostasis , Real-Time Polymerase Chain Reaction , Alzheimer’s Disease, }, references={}, document_type={Journal Article, }, affiliation={Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli, Italy., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli, Italy., Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli, Italy. Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54478, author={Bruckmann C, Tamburri S, De Lorenzi V, Doti N, Monti A, Mathiasen L, Cattaneo A, Ruvo M, Bachi A, Blasi F}, title={Mapping the native interaction surfaces of PREP1 with PBX1 by cross-linking mass-spectrometry and mutagenesis}, date={2020 Oct 8}, journal={Sci Rep (ISSN: 2045-2322linking, 2045-2322electronic)}, year={2020}, fullvolume={48}, volume={48}, pages={16809--16809}, url={}, abstract={Both onco-suppressor PREP1 and the oncogene MEIS1 bind to PBX1. This interaction stabilizes the two proteins and allows their translocation into the nucleus and thus their transcriptional activity. Here, we have combined cross-linking mass-spectrometry and systematic mutagenesis to detail the binding geometry of the PBX1-PREP1 (and PBX1-MEIS1) complexes, under native in vivo conditions. The data confirm the existence of two distinct interaction sites within the PBC domain of PBX1 and unravel differences among the highly similar binding sites of MEIS1 and PREP1. The HR2 domain has a fundamental role in binding the PBC-B domain of PBX1 in both PREP1 and MEIS1. The HR1 domain of MEIS1, however, seem to play a less stringent role in PBX1 interaction with respect to that of PREP1. This difference is also reflected by the different binding affinity of the two proteins to PBX1. Although partial, this analysis provides for the first time some ideas on the tertiary structure of the complexes not available before. Moreover, the extensive mutagenic analysis of PREP1 identifies the role of individual hydrophobic HR1 and HR2 residues, both in vitro and in vivo.}, keywords={A549 Cells, Binding Sites, Cloning, Molecular, Enzyme-Linked Immunosorbent Assay, Homeodomain Proteins Metabolism, Humans, Mass Spectrometry, Mutagenesis, Myeloid Ecotropic Viral Integration Site 1 Protein Metabolism, Pre-B-Cell Leukemia Transcription Factor 1 Metabolism, Protein Interaction Mapping Methods, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={IFOM (Foundation FIRC Institute of Molecular Oncology), Via Adamello 16, 20139, Milan, Italy. chiara.bruckmann@ifom.eu. Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139, Milan, Italy. Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56124, Pisa, Italy. Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone 16, 80134, Naples, Italy. Cogentech S.R.L. Benefit Corporation IT, Via Adamello 16, 20139, Milan, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54797, author={Smaldone G, Caruso D, Sandomenico A, Iaccarino E, Focà A, Ruggiero A, Ruvo M, Vitagliano L}, title={Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions}, date={2021 Oct 2}, journal={Int J Mol Sci (ISSN: 1422-0067linking)}, year={2021}, fullvolume={8}, volume={8}, pages={N/D--N/D}, url={}, abstract={The three members (GADD45α, GADD45β, and GADD45γ) of the growth arrest and DNA damage-inducible 45 (GADD45) protein family are involved in a myriad of diversified cellular functions. With the aim of unravelling analogies and differences, we performed comparative biochemical and biophysical analyses on the three proteins. The characterization and quantification of their binding to the MKK7 kinase, a validated functional partner of GADD45β, indicate that GADD45α and GADD45γ are strong interactors of the kinase. Despite their remarkable sequence similarity, the three proteins present rather distinct biophysical properties. Indeed, while GADD45β and GADD45γ are marginally stable at physiological temperatures, GADD45α presents the Tm value expected for a protein isolated from a mesophilic organism. Surprisingly, GADD45α and GADD45β, when heated, form high-molecular weight species that exhibit features (ThT binding and intrinsic label-free UV/visible fluorescence) proper of amyloid-like aggregates. Cell viability studies demonstrate that they are endowed with a remarkable toxicity against SHSY-5Y and HepG2 cells. The very uncommon property of GADD45β to form cytotoxic species in near-physiological conditions represents a puzzling finding with potential functional implications. Finally, the low stability and/or the propensity to form toxic species of GADD45 proteins constitute important features that should be considered in interpreting their many functions.}, keywords={Amyloid Chemistry Metabolism , Cell Survival , Cultured , Humans , Intracellular Signaling Peptides And Proteins Chemistry Genetics Metabolism , Map Kinase Kinase 7 Metabolism , Protein Aggregates , Protein Aggregation, Pathological Metabolism , Protein Binding , Protein Conformation, Beta-Strand , Protein Stability , Recombinant Proteins , Thermodynamics , Amyloid-Like Toxicity , Structure-Stability Relationships}, references={}, document_type={Journal Article}, affiliation={IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Napoli, Italy. Institute of Biostructures and Bioimaging, C.N.R., Via Mezzocannone 16, 80134 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54802, author={Tagliamonte M, Mauriello A, Cavalluzzo B, Ragone C, Manolio C, Luciano A, Barbieri A, Palma G, Scognamiglio G, Di Mauro A, Di Bonito M, Tornesello ML, Buonaguro FM, Vitagliano L, Caporale A, Ruvo M, Buonaguro L}, title={MHC-Optimized Peptide Scaffold for Improved Antigen Presentation and Anti-Tumor Response}, date={2021 Oct 20}, journal={Front Immunol (ISSN: 1664-3224linking)}, year={2021}, fullvolume={5}, volume={5}, pages={769799--769799}, url={}, abstract={Tumor Associated Antigens (TAAs) may suffer from an immunological tolerance due to expression on normal cells. In order to potentiate their immunogenicity, heteroclitic peptides (htcPep) were designed according to prediction algorithms. In particular, specific modifications were introduced in peptide residues facing to TCR. Moreover, a MHC-optimized scaffold was designed for improved antigen presentation to TCR by H-2Db allele. The efficacy of such htcPep was assessed in C57BL/6 mice injected with syngeneic melanoma B16F10 or lung TC1 tumor cell lines, in combination with metronomic chemotherapy and immune checkpoint inhibitors. The immunogenicity of htcPep was significantly stronger than the corresponding wt peptide and the modification involving both MHC and TCR binding residues scored the strongest. In particular, the H-2Db-specific scaffold significantly potentiated the peptides' immunogenicity and control of tumor growth was comparable to wt peptide in a therapeutic setting. Overall, we demonstrated that modified TAAs show higher immunogenicity compared to wt peptide. In particular, the MHC-optimized scaffold can present different antigen sequences to TCR, retaining the conformational characteristics of the corresponding wt. Cross-reacting CD8(+) T cells are elicited and efficiently kill tumor cells presenting the wild-type antigen. This novel approach can be of high clinical relevance in cancer vaccine development.}, keywords={Taa, Cancer Vaccine, Heteroclitic Peptides, Major Histocompatibility Complex I (mhci), Peptide Scaffold}, references={}, document_type={Journal Article}, affiliation={Innovative Immunological Models Lab, Istituto Nazionale Tumori - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - "Fond G. Pascale", Naples, Italy. Animal Facility, Istituto Nazionale Tumori - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - "Fond G. Pascale", Naples, Italy. Pathology Unit, Istituto Nazionale Tumori - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - "Fond G. Pascale", Naples, Italy. Molecular Biology and Viral Oncogenesis, Istituto Nazionale Tumori - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - "Fond G. Pascale", Naples, Italy. Institute of Biostructures and Bioimaging, Consiglio Nazionale delle Ricerche (CNR), Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53621, author={Aliberti A, Ricciardi A, Giaquinto M, Micco A, Bobeico E, La Ferrara V, Ruvo M, Cutolo A, Cusano A}, title={Microgel assisted Lab-on-Fiber Optrode}, date={2017 Oct 31}, journal={Sci Rep (ISSN: 2045-2322, 2045-2322electronic, 2045-2322linking)}, year={2017}, fullvolume={213}, volume={213}, pages={14459--14459}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032619015&doi=10.1038%2fs41598-017-14852-5&partnerID=40&md5=121e8670d2cfba52b08d642a303e3be9}, abstract={ Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.}, keywords={Optrode, Microgel Assisted, Lab On Fiber, }, references={}, document_type={Journal Article, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, I-82100, Benevento, Italy., ENEA, Portici Research Center, P.le E. Fermi 1, I-80055 Portici, Napoli, Italy., Institute of Biostructure and Bioimaging, National Research Council, I-80143, Napoli, Italy., Optoelectronics Group, Department of Engineering, University of Sannio, I-82100, Benevento, Italy. a.cusano@unisannio.it., }, ibbaffiliation={1}, } @article{IBB_ID_54083, author={Giaquinto M, Micco A, Aliberti A, Ricciardi A, Ruvo M, Cutolo A, Cusano A}, title={Microgel photonics and lab on fiber technology for advanced label-free fiber optic nanoprobes}, date={2016}, journal={Proc Spie Int Soc Opt Eng (ISSN: 0277-786x9781510602199)}, year={2016}, fullvolume={192}, volume={192}, pages={N/D--N/D}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-84976531501&doi=10.1117%2f12.2236829&partnerID=40&md5=330601a82012b77a0a5e7c8445877c49}, abstract={We experimentally demonstrate a novel optical fiber label free optrode platform resulting from the integration between two rapidly emerging technologies such as Lab-on-Fiber Technology (LOFT) and Microgel Photonics (MPs). The device consists of a microgel (MG) layer painted on a metallic slabs supporting plasmonic resonances, directly integrated on the optical fiber tip. A molecular binding event induces significant changes in the MG layer thickness (and consequently in its 'equivalent' refractive index) resulting in an evident wavelength shift of the resonant feature. As a case of study, glucose-responsive MGs have been synthesized by incorporating into the gel matrix boronic acid moieties, whose interaction with glucose rules the driving forces for gel swelling. Our results pave the way for new technological routes aimed to develop advanced label free fiber optic nanoprobes. © 2016 SPIE.}, keywords={Biosensors, Glucose, Lab-On-Fiber Technology, Microgel, Optical Fiber Sensors, Plasmonics, Fiber Optic Sensors, Nanoprobes, Refractive Index, Emerging Technologies, Fiber-Optic Nanoprobe, Glucose-Responsive, Plasmonic Resonances, Technological Route, }, references={Ricciardi, A., Crescitelli, A., Vaiano, P., Quero, G., Consales, M., Pisco, M., Esposito, E., Cusano, A., Lab-onfiber technology: A new vision for chemical and biological sensing (2015) Analyst, 140 (24), pp. 8068-807 Cusano, A., Consales, M., Crescitelli, A., Ricciardi, A., Lab-on-fiber technology (2014) Springer Series in Surface Sciences Manikas, A., Aliberti, A., Causa, F., Battista, E., Netti, P.A., Thermoresponsive PNIPAAm hydrogel scaffolds with encapsulated AuNPs show high analytetrapping ability and tailored plasmonic properties for high sensing efficiency (2015) J. Mater. Chem. B, 3, pp. 53-58 Guan, Y., Zhang, Y., Boronic acid-containing hydrogels: Synthesis and their applications (2013) Chem. Soc. Rev, 42 (20), pp. 8106-8121 Sorrell, C.D., Serpe, M.J., Glucose sensitive poly (N-isopropylacrylamide) microgel based etalons (2012) Anal BioanalChem, 402 (7), pp. 2385-2393 Toma, M., Jonas, U., Mateescu, A., Knoll, W., Dostalek, J., Active control of spr by thermoresponsive hydrogels for biosensor applications (2013) Phys. Chem. C, 117 (22), pp. 11705-11712 Mesch, M., Zhang, C., Braun, P.V., Giessen, H., Functionalized hydrogel on plasmonic nanoantennas for noninvasive glucose sensing (2015) ACS Photonics, 2 (4), pp. 475-480}, document_type={Conference, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, I-82100, Italy Institute of Biostructure and Bioimaging, National Research Council, Napoli, I-80143, Italy}, ibbaffiliation={1}, } @article{IBB_ID_9194, author={Ponticelli S, Marasco D, Tarallo V, Albuquerque RJC, Mitola S, Takeda A, Stassen J, Presta M, Ambati J, Ruvo M, De Falco S}, title={Modulation of Angiogenesis by a Tetrameric Tripeptide That Antagonizes Vascular Endothelial Growth Factor Receptor}, date={2008 Dec 5}, journal={Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking)}, year={2008}, fullvolume={458}, volume={458}, pages={34250--34259}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-57749085669&partnerID=40&md5=4d8a1de59ec7cfb1ec92a94bfca4aa3b}, abstract={Vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) is involved in complex biological processes often associated to severe pathological conditions like cancer, inflammation, and metastasis formation. Consequently, the search for antagonists of Flt-1 has recently gained a growing interest. Here we report the identification of a tetrameric tripeptide from a combinatorial peptide library built using non-natural amino acids, which binds Flt-1 and inhibits in vitro its interaction with placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) A and B (IC(50) similar to 10 mu M). The peptide is stable in serum for 7 days and prevents both Flt-1 phosphorylation and the capillary-like tube formation of human primary endothelial cells stimulated by PlGF or VEGF-A. Conversely, the identified peptide does not interfere in VEGF-induced VEGFR-2 activation. In vivo, this peptide inhibits VEGF-A- and PlGF-induced neoangiogenesis in the chicken embryo chorioallantoic membrane assay. In contrast, in the cornea, where avascularity is maintained by high levels of expression of the soluble form of Flt-1 receptor (sFlt-1) that prevents the VEGF-A activity, the peptide is able to stimulate corneal mouse neovascularization in physiological condition, as reported previously for others neutralizing anti-Flt-1 molecules. This tetrameric tripeptide represents a new, promising compound for therapeutic approaches in pathologies where Flt-1 activation plays a crucial role.}, keywords={Amines, Amino Acids, Bioactivity, Growth (materials), Modulation, Organic Acids, Pathology, Peptides, Self Assembly, Theorem Proving, Angiogenesis, Biological Processes, Chicken Embryos, Chorioallantoic Membranes, Growth Factors, In Vitro, In-Vivo, Natural Amino Acids, Neoangiogenesis, Neovascularization, Pathological Conditions, Peptide Libraries, Physiological Conditions, Tri Peptides, Tube Formations, Vascular Endothelial Growth Factor Receptors, Vegfr-2, Endothelial Cells, Placental Growth Factor, Tetramer, Tripeptide, Vasculotropin A, Vasculotropin Receptor 1, Animal Experiment, Animal Model, Animal Tissue, Antiangiogenic Activity, Article, Chick Embryo, Combinatorial Library, Controlled Study, Cornea Neovascularization, Drug Receptor Binding, Endothelium Cell, Human, Human Cell, In Vivo Study, Mouse, Nonhuman, Priority Journal, Protein Phosphorylation, Receptor Upregulation, Combinatorial Chemistry Techniques, Gene Expression Regulation, Inhibitory Concentration 50, Inbred Balb C, }, references={Yancopoulos, G.D., Davis, S., Gale, N.W., Rudge, J.S., Wiegand, S.J., Holash, J., (2000) Nature, 407, pp. 242-24 Olsson, A.K., Dimberg, A., Kreuger, J., Claesson-Welsh, L., (2006) Nat. 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Med, 196, pp. 1497-1506}, document_type={Journal Article, }, affiliation={Angiogenesis Laboratory and Stem Cell Fate Laboratory, Institute of Genetics and Biophysics Adriano Buzzati-Traverso, Consiglio Nazionale Delle Ricerche (CNR), 80131 Napoli, Italy Institute of Biostructures and Bioimaging, CNR, 80134 Napoli, Italy Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, United States Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy Thrombogenics, Campus Gasthuisberg, B-3000 Leuven, Belgium}, ibbaffiliation={1}, } @article{IBB_ID_52208, author={Farina B, Doti N, Pirone L, Malgieri G, Pedone E, Ruvo M, Fattorusso R}, title={Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of phospholipase D1 revealed by NMR spectroscopy}, date={2013 Sep}, journal={Bba-Gen Subjects (ISSN: 1570-9639, 0006-3002, 0925-4439)}, year={2013}, fullvolume={443}, volume={443}, pages={1572--1580}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879048177&partnerID=40&md5=512e21ff48bb8d4814830568aa75948a}, abstract={PED/PEA15 is a small protein involved in many protein-protein interactions that modulates the function of a number of key cellular effectors involved in major cell functions, including apoptosis, proliferation and glucose metabolism. In particular, PED/PEA15 interacts with the phospholipase D (PLD) isoforms 1 and 2 increasing protein kinase C-alpha isoform activity and affects both insulin-stimulated glucose transport and glucose-stimulated insulin secretion. The C-terminal portion (residues 712-1074) of PLD1, named D4, is still able to interact with PED/PEA15. In this study we characterized, by means of NMR spectroscopy, the molecular interaction of PED/PEA15 with D4 alpha, a smaller region of D4, encompassing residues 712-818, shown to have the same affinity for PED/PEA15 and to induce the same effects as D4 in PED/PEA15-overexpressing cells. Chemical shift perturbation (CSP) studies allowed to define D4 alpha binding site of PED/PEA15 and to identify a smaller region likely affected by an allosteric effect. Moreover, ELISA-like experiments showed that three 20-mer overlapping synthetic peptides, covering the 762-801 region of D4 alpha, strongly inhibit PED/PEA15-D4 alpha interaction through their binding to PED/PEA15 with K(D)s in low micromolar range. Finally, molecular details of the interaction of PED/PEA15 with one of the three peptides have been revealed by CSP and saturation transfer difference (STD) analyses. (C) 2013 Elsevier B.V. All rights reserved.}, keywords={Chemical Shift Perturbation, Death Domain, Ped Pea15 Protein, Protein-Protein Interaction, D4 Alpha Protein, Phospholipase D1, Phosphoprotein, Phosphoprotein Enriched In Astrocyte 15, Phosphoprotein Enriched In Diabetes, Protein Kinase C Alpha, Synthetic Peptide, Unclassified Drug, Human, Peptide Fragment, Signal Peptide, Allosterism, Article, Binding Site, Controlled Study, Enzyme Activity, Enzyme Linked Immunosorbent Assay, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Protein Analysis, Protein Binding, Protein Expression, Protein Protein Interaction, Chemistry, Metabolism, Protein Conformation, Enzyme-Linked Immunosorbent Assay, Intracellular Signaling Peptides And Proteins, Intracellular Signaling Peptides And Proteins Chemistry Metabolism, Peptide Fragments Chemistry Metabolism, Phospholipase D Chemistry Metabolism, Phosphoproteins Chemistry Metabolism, }, references={Araujo, H., Danziger, N., Cordier, J., Glowinski, J., Chneiweiss, H., Characterization of PEA-15, a major substrate for protein kinase C in astrocytes (1993) Journal of Biological Chemistry, 268 (8), pp. 5911-592 Estelles, A., Yokoyama, M., Nothias, F., Vincent, J.-D., Glowinski, J., Vernier, P., Chneiweiss, H., The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs conserved on their full length in mouse and human (1996) Journal of Biological Chemistry, 271 (25), pp. 14800-14806. , DOI 10.1074/jbc.271.25.14800 Hill, J.M., Vaidyanathan, H., Ramos, J.W., Ginsberg, M.H., Werner, M.H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) EMBO Journal, 21 (23), pp. 6494-6504. , DOI 10.1093/emboj/cdf641 Twomey, E.C., Wei, Y., High-definition NMR structure of PED/PEA-15 death effector domain reveals details of key polar side chain interactions (2012) Biochem. 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Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, via Vivaldi 43, 81100}, ibbaffiliation={1}, } @article{IBB_ID_54267, author={Miceli M, Cutignano A, Conte M, Ummarino R, Romanelli A, Ruvo M, Leone M, Mercurio FA, Doti N, Manzo E, Romano G, Altucci L, Ianora A}, title={Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells}, date={2019 Nov 1}, journal={Mar Drugs (ISSN: 1660-3397linking)}, year={2019}, fullvolume={135}, volume={135}, pages={N/D--N/D}, url={}, abstract={Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells.}, keywords={Ms , Nmr , Skeletonema Marinoi , Bioactive Lipids , Cytotoxic Activity , Diatoms, Antineoplastic Agents Pharmacology , Apoptosis Drug Effects , Caspase 3 Metabolism , Caspase 7 Metabolism , Cell Cycle Drug Effects , Cell Survival Drug Effects , Diatoms Chemistry , Humans , Microalgae, }, references={}, document_type={Journal Article, }, affiliation={CEINGE-Biotecnologie Avanzate s.c.ar.l., 80145 Naples, Italy. micelim@ceinge.unina.it. CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, Pozzuoli, 80078 Naples, Italy. acutignano@icb.cnr.it. Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via L. De Crecchio 7, 80138 Naples, Italy. mariarosaria.conte@unicampania.it. Institute of Biostructures and Bioimaging (IBB-CNR), Via Mezzocannone 16, 80134 Naples, Italy. raffaella.u@libero.it. Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. raffaella.u@libero.it. Department of Pharmaceutical Sciences, University of Milan, via Venezian 21, 20133 Milan, Italy. alessandra.romanelli@unimi.it.}, ibbaffiliation={1}, } @article{IBB_ID_53303, author={Sandomenico A, Focà A, Sanguigno L, Caporale A, Focà G, Pignalosa A, Corvino G, Caragnano A, Beltrami AP, Antoniali G, Tell G, Leonardi A, Ruvo M}, title={Monoclonal antibodies against pools of mono- and polyacetylated peptides selectively recognize acetylated lysines within the context of the original antigen}, date={2016 Aug}, journal={Mabs-Austin (ISSN: 1942-0862)}, year={2016}, fullvolume={213}, volume={213}, pages={1575--1589}, url={}, abstract={Post-translational modifications (PTMs) strongly influence the structure and function of proteins. Lysine side chain acetylation is one of the most widespread PTMs, and it plays a major role in several physiological and pathological mechanisms. Protein acetylation may be detected by mass spectrometry (MS), but the use of monoclonal antibodies (mAbs) is a useful and cheaper option. Here, we explored the feasibility of generating mAbs against single or multiple acetylations within the context of a specific sequence. As a model, we used the unstructured N-terminal domain of APE1, which is acetylated on Lys27, Lys31, Lys32 and Lys35. As immunogen, we used a peptide mixture containing all combinations of single or multi-acetylated variants encompassing the 24-39 protein region. Targeted screening of the resulting clones yielded mAbs that bind with high affinity to only the acetylated APE1 peptides and the acetylated protein. No binding was seen with the non-acetylated variant or unrelated acetylated peptides and proteins, suggesting a high specificity for the APE1 acetylated molecules. MAbs could not finely discriminate between the differently acetylated variants; however, they specifically bound the acetylated protein in mammalian cell extracts and in intact cells and tissue slices from both breast cancers and from a patient affected by idiopathic dilated cardiomyopathy. The data suggest that our approach is a rapid and cost-effective method to generate mAbs against specific proteins modified by multiple acetylations or other PTMs.}, keywords={Acetylation, Anti-Acetyl-Peptide Monoclonal Antibodies, Peptide Libraries, Ape1, Ref-1, Acetylated-Ape1, Human Apurinic, Apyrimidinic Endonuclease-1, N-Terminal Domain, Protein, Binding, Cells, Inhibition, Metabolism, Interacts, }, references={}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (IBB-CNR), Napoli, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Napoli, Italy; Bioker Multimedica, Napoli, Italy; }, ibbaffiliation={1}, } @article{IBB_ID_54443, author={Sivaccumar J, Sandomenico A, Vitagliano L, Ruvo M}, title={Monoclonal Antibodies: A Prospective and Retrospective View}, date={2021}, journal={Curr Med Chem (ISSN: 0929-8673linking, 1875-533xelectronic)}, year={2021}, fullvolume={51}, volume={51}, pages={435--471}, url={}, abstract={BACKGROUND: Monoclonal antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, angiogenesis-related diseases and more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering. OBJECTIVES: The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends. RESULTS: We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables. CONCLUSIONS: The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.}, keywords={Antibodies Format, Biotherapeutics, Monoclonal Antibody, Targeted Cancer Therapy, Therapeutic Use, Biological Products, Humans, Prospective Studies, Protein Engineering, Retrospective Studies, Therapeutic Monoclonal Antibodies, Antibody Modeling Softwares, Antibody Developmental Technologies, Antibody Engineering, Diseases, Pharmacological Therapies, Monoclonal Therapeutic Use}, references={}, document_type={Journal Article, Review}, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone, 16, 80134, Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54293, author={Canassa-deleo T, Campo VL, Rodrigues LC, Marchiori MF, Fuzo C, Brigido MM, Sandomenico A, Ruvo M, Maranhao AQ, Dias-baruffi M}, title={Multifaceted antibodies development against synthetic alpha-dystroglycan mucin glycopeptide as promising tools for dystroglycanopathies diagnostic}, date={2020 Feb}, journal={Glycoconj J (ISSN: 0282-0080linking)}, year={2020}, fullvolume={141}, volume={141}, pages={77--93}, url={}, abstract={Dystroglycanopathies are diseases characterized by progressive muscular degeneration and impairment of patient's quality of life. They are associated with altered glycosylation of the dystrophin-glycoprotein (DGC) complex components, such as alpha-dystroglycan (alpha-DG), fundamental in the structural and functional stability of the muscle fiber. The diagnosis of dystroglycanopathies is currently based on the observation of clinical manifestations, muscle biopsies and enzymatic measures, and the available monoclonal antibodies are not specific for the dystrophic hypoglycosylated muscle condition. Thus, modified alpha-DG mucins have been considered potential targets for the development of new diagnostic strategies toward these diseases. In this context, this work describes the synthesis of the hypoglycosylated alpha-DG mimetic glycopeptide NHAc-Gly-Pro-Thr-Val-Thr[alphaMan]-Ile-Arg-Gly-BSA (1) as a potential tool for the development of novel antibodies applicable to dystroglycanopathies diagnosis. Glycopeptide 1 was used for the development of polyclonal antibodies and recombinant monoclonal antibodies by Phage Display technology. Accordingly, polyclonal antibodies were reactive to glycopeptide 1, which enables the application of anti-glycopeptide 1 antibodies in immune reactive assays targeting hypoglycosylated alpha-DG. Regarding monoclonal antibodies, for the first time variable heavy (VH) and variable light (VL) immunoglobulin domains were selected by Phage Display, identified by NGS and described by in silico analysis. The best-characterized VH and VL domains were cloned, expressed in E. coli Shuffle T7 cells, and used to construct a single chain fragment variable that recognized the Glycopeptide 1 (GpalphaDG1 scFv). Molecular modelling of glycopeptide 1 and GpalphaDG1 scFv suggested that their interaction occurs through hydrogen bonds and hydrophobic contacts involving amino acids from scFv (I51, Y33, S229, Y235, and P233) and R8 and alpha-mannose from Glycopeptide 1.}, keywords={Antibodies, Glycopeptide, Mucins, Phage Display, Molecular Modelling, Alpha-Dystroglycan, α-Dystroglycan, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. Cafe S/N, CEP, Ribeirao Preto, SP, 14040-903, Brazil. Centro Universitario Barao de Maua, Rua Ramos de Azevedo 423, Jardim Paulista, CEP, Ribeirao Preto, 14090-180, SP, Brazil. Instituto de Ciencias Biologicas, Universidade de Brasilia, Asa Norte, Brasilia, DF, CEP 70910-900, Brazil. Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone, 16, 80134, Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_10963, author={De Falco S, Ruvo M, Verdoliva A, Scarallo A, Raimondo D, Raucci A, Fassina G}, title={N-terminal myristylation of HBV preS1 domain enhances receptor recognition}, date={2001 May}, journal={J Pept Res (ISSN: 1397-002x, 1397-002xlinking)}, year={2001}, fullvolume={417}, volume={417}, pages={390--400}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034885524&partnerID=40&md5=4e286bbf02f2978f6fe25d1ed64fe8cc}, abstract={The N-terminal portion of the large envelope protein of the human hepatitis B virus (HBV), the preS1 domain, plays a fundamental role in cell attachment and infectivity. Recent investigations have suggested that myristylation of preS1 Gly2 residue is essential for viral infectivity, but the importance of this post-translational modification on HBV-receptor interaction has not been elucidated completely. In this study we produced, using stepwise solid-phase chemical synthesis, the entire preS1[1-119] domain (adw2 subtype), and compared its receptor binding activity with the myristylated form, myristyl-preS1[2-119] in order to define the importance of fatty acid modification. Both synthetic proteins were fully characterized in terms of structural identity using TOF-MALDI mass spectrometry and analysis of tryptic fragments. Circular dichroism measurements indicated a low content of ordered structure in the preS1 protein, while the propensity of the myristylated derivative to assume a conformationally defined structure was more evident. HBV-receptor binding assays performed with plasma membranes preparations from the hepatocyte carcinoma cell line HepG2 clearly showed that the preS1[1-119] domain recognizes the HBV receptor, and confirmed that binding is occurring through the 21-47 region. The myristylated derivative recognized HBV receptor preparations with higher affinity than the preS1 domain, suggesting that the conformational transitions induced in the preS1 moiety by fatty acid post-translational modification are important for efficient attachment of viral particles to HBV receptors.}, keywords={Hepatitis B Virus, Myristylation, Pres1, Receptor Binding, Virus Envelope Protein, Amino Terminal Sequence, Article, Binding Affinity, Circular Dichroism, Human, Human Cell, Mass Spectrometry, Priority Journal, Protein Conformation, Protein Domain, Protein Interaction, Protein Processing, Protein Structure, Protein Synthesis, Virus Adsorption, Virus Infectivity, Amino Acid Sequence, Cell Line, Chromatography, High Pressure Liquid, Enzyme-Linked Immunosorbent Assay, Hepatitis B Surface Antigens, Molecular Sequence Data, Myristic Acid, Protein Precursors, Matrix-Assisted Laser Desorption-Ionization, Chemistry, Metabolism, }, references={Ganem, D., Varmus, H.E., The molecular biology of the hepatitis B viruses (1987) Annu. Rev. Biochem., 56, pp. 651-69 Tiollais, P., Poucel, C., Dejean, A., The hepatitis B virus (1985) Nature, 317, pp. 489-495 Neurath, A.R., Kent, S.B.H., The pre-S region of hepadnavirus envelope protein (1988) Adv. Virus. Res., 34, pp. 65-142 Le Seyec, J., Chouteau, P., Cannie, I., Guguen-Guillouzo, C., Gripon, P., Infection process of the hepatitis B virus depends on the presence of a defined sequence in the preS1 domain (1999) J. Virol., 73, pp. 2052-2057 Petit, M.A., Dubanchet, S., Capel, F., Voet, P., Dauguet, C., Hauser, P., hepG2 cell binding activities of different hepatitis B virus isolates: Inhibitory effect of anti-HBs and anti preS1 (21-47) (1991) Virology, 180, pp. 483-491 Pontisso, P., Ruvoletto, M.G., Tribelli, C., Gerlich, W.H., Ruol, A., Alberti, A., The preS1 domain of hepatitis B virus and IgA cross-react in their binding to the hepatocyte surface (1992) J. Gen. Virol., 73, pp. 2041-2045 Gripon, P., Le Seyec, J., Rumin, S., Guguen-Gillouzo, C., Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity (1996) Virology, 213, pp. 292-299 Bruss, V., Haglestein, J., Gerhardt, E., Galle, P.R., Myristilation of the large surface protein is required for hepatitis B virus in vitro infectivity (1996) Virology, 218, pp. 396-399 Rhee, S.S., Hunter, E., Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsid (1987) J. Virol., 61, pp. 1045-1053 Rein, A., McClure, M.R., Rice, N.R., Luftig, R.B., Shultz, A.M., Myristylation site in Pr65gag is essential for virus particle formation by moloney murine leukemia virus (1986) Proc. Natl. Acad. Sci. USA, 83, pp. 7246-7250 Chow, M., Newman, J.F.E., Filman, D., Hogle, J.M., Rowlands, D.J., Brown, F., Myristylation of picornavirus capsid protein VP4 and its structural significance (1987) Nature, 327, pp. 482-486 Krausslich, H.G., Holscher, C., Reuer, Q., Harber, J., Wimmer, E., Myristoylation of the poliovirus polyprotein is required for proteolytic processing of the capsid and for viral infectivity (1990) J. Virol., 64, pp. 2433-2436 Streuli, C.H., Griffin, B.E., Myristic acid is coupled to a structural protein of polyoma virus and SV40 (1987) Nature, 326, pp. 619-621 Bruss, V., Ganem, D., The role of envelope proteins in hepatitis B virus assembly (1991) Proc. Natl. Acad. Sci. 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Acta, 173, pp. 183-192 Aden, D.P., Fogel, A., Plotkin, S., Damjanov, I., Knowles, B., Controlled synthesis oh HBsAg in a differentiated human liver carcinoma-derived cell line (1979) Nature, 282, pp. 615-616 Dash, S., Rao, K.V.S., Panda, S., Receptor for Pre-S1 (21-47) component of hepatitis B virus on the liver cells (1992) J. Med. Virol., 37, pp. 116-121 Ryu, C.J., Cho, D.Y., Gripon, P., Kim, H.S., Guguen-Guillouzo, C., Hong, H.J., An 80-kilodalton protein that binds to the PreS1 domain of hepatitis B virus (2000) J. Virol., 74, pp. 110-116 Persing, D.H., Varmus, H.E., Ganem, D., The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid (1987) J. Virol., 61, pp. 1672-1677 Towler, D.A., Gordon, J.I., The biology and enzymology of eukaryotic protein acylation (1988) Annu. Rev. Biochem., 57, pp. 69-99 Bruss, V., Lu, X., Thomssen, R., Gerlich, W.H., Post-translational alterations in transmembrane topology of the hepatitis B virus large envelope protein (1994) EMBO J., 13, pp. 2273-2279 Schnoelzer, M., Kent, S.B.H., Constructing proteins by dovetailing unprotected synthetic peptides: Backbone-engineered HIV protease (1992) Science, 256, pp. 221-225 Dawson, P.E., Muir, T.W., Clark-Lewis, I., Kent, S.B.H., Synthesis of proteins by native chemical ligation (1994) Science, 266, pp. 776-779 Ostapchuk, P., Hearing, P., Ganem, D., A dramatic shift in the transmembrane topology of a viral envelope glycoprotein accompanies hepatitis B viral morphogenesis (1994) EMBO J., 13, pp. 1048-4057 Bruss, V., Thomssen, R., Mapping a region of the large envelope protein required for hepatitis B virus maturation (1994) J. Virol., 68, pp. 1643-1650 Neurath, A. R., Kent, S. B. H., The pre-S region of hepadnavirus envelope protein (1988) Adv. Virus. Res., 34, pp. 65-142 Petit, M. A., Dubanchet, S., Capel, F., Voet, P., Dauguet, C., Hauser, P., hepG2 cell binding activities of different hepatitis B virus isolates: Inhibitory effect of anti-HBs and anti preS1 (21-47) (1991) Virology, 180, pp. 483-491 Rhee, S. S., Hunter, E., Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsid (1987) J. Virol., 61, pp. 1045-1053 Krausslich, H. G., Holscher, C., Reuer, Q., Harber, J., Wimmer, E., Myristoylation of the poliovirus polyprotein is required for proteolytic processing of the capsid and for viral infectivity (1990) J. Virol., 64, pp. 2433-2436 Streuli, C. H., Griffin, B. E., Myristic acid is coupled to a structural protein of polyoma virus and SV40 (1987) Nature, 326, pp. 619-621 Macrrae, D. R., Bruss, V., Ganem, D., Myristylation of a duck hepatitis B virus envelope protein is essential for infectivity but not for virus assembly (1991) Virology, 181, pp. 359-363 Hubbard, A. L., Wall, D. A., Ma, A., Isolation of rat hepatocyte plasma membranes. Presence of the three major domain (1983) J. Cell. Biol., 96, pp. 217-229 Aden, D. P., Fogel, A., Plotkin, S., Damjanov, I., Knowles, B., Controlled synthesis oh HBsAg in a differentiated human liver carcinoma-derived cell line (1979) Nature, 282, pp. 615-616 Dash, S., Rao, K. V. S., Panda, S., Receptor for Pre-S1 (21-47) component of hepatitis B virus on the liver cells (1992) J. Med. Virol., 37, pp. 116-121 Ryu, C. J., Cho, D. Y., Gripon, P., Kim, H. S., Guguen-Guillouzo, C., Hong, H. J., An 80-kilodalton protein that binds to the PreS1 domain of hepatitis B virus (2000) J. Virol., 74, pp. 110-116 Persing, D. H., Varmus, H. E., Ganem, D., The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid (1987) J. Virol., 61, pp. 1672-1677 Towler, D. A., Gordon, J. I., The biology and enzymology of eukaryotic protein acylation (1988) Annu. Rev. Biochem., 57, pp. 69-99 Dawson, P. E., Muir, T. W., Clark-Lewis, I., Kent, S. B. H., Synthesis of proteins by native chemical ligation (1994) Science, 266, pp. 776-779}, document_type={Journal Article, }, affiliation={Biopharmaceuticals, TECNOGEN S.C.p.A, Piana di Monte Verna, Italy Biopharmaceuticals TECNOGEN S.C.p.A, 81015 Piana di Monte Verna (CE), Italy}, ibbaffiliation={1}, } @article{IBB_ID_52857, author={Foca A, Sanguigno L, Foca G, Strizzi L, Iannitti R, Palumbo R, Hendrix MJ, Leonardi A, Ruvo M, Sandomenico A}, title={New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding}, date={2015 Sep 7}, journal={Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking)}, year={2015}, fullvolume={257}, volume={257}, pages={21342--21362}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84941253823&partnerID=40&md5=31fdd8a3c0d1446c51ef33c556456eeb}, abstract={Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention. © 2015 by the authors; licensee MDPI, Basel, Switzerland.}, keywords={Fab Fragments, Melanoma, Monoclonal Antibody, Nodal, Antigen, Cripto 1, Protein Nodal, Receptor, Smad2 Protein, Smad3 Protein, Unclassified Drug, Antibody Specificity, Antibody Titer, Article, Blood Analysis, Controlled Study, Deglycosylation, Enzyme Linked Immunosorbent Assay, Epitope Mapping, Female, Fluorescence Activated Cell Sorting, Human, Human Cell, Hybridoma, Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry, Mouse, Nonhuman, Protein Analysis, Protein Binding, Protein Degradation, Protein Phosphorylation, Solid Phase Synthesis, Surface Plasmon Resonance, Western Blotting, Fab Fragments Monoclonal Antibody Melanoma Nodal Spr, Amino Acid Sequence , Antibodies, Monoclonal Chemistry Pharmacology , Epitope Mapping Methods , Epitopes Chemistry Metabolism , Gpi-Linked Proteins Chemistry Metabolism , Growth Differentiation Factors Chemistry , Immunoglobulin Fab Fragments Chemistry Metabolism , Intercellular Signaling Peptides And Proteins Chemistry Metabolism , Models, Molecular , Molecular Sequence Data , Neoplasm Proteins Chemistry Metabolism , Nodal Protein Antagonists, Inhibitors Chemistry Metabolism , Peptides Chemical Synthesis Chemistry Isolation, Purification Metabolism , Protein Structure, Secondary, }, references={Schier, A.F., Nodal signaling in vertebrate development (2003) Annu. Rev. Cell Dev. Biol, 19, pp. 589-62 Shen, M.M., Nodal signaling: Developmental roles and regulation (2007) Development, 134, pp. 1023-1034 Strizzi, L., Hardy, K.M., Kirschmann, D.A., Ahrlund-Richter, L., Hendrix, M.J., Nodal expression and detection in cancer: Experience and challenges (2012) Cancer Res, 72, pp. 1915-1920 Strizzi, L., Postovit, L.M., Margaryan, N.V., Lipavsky, A., Gadiot, J., Blank, C., Seftor, R.E., Hendrix, M.J., Nodal as a biomarker for melanoma progression and a new therapeutic target for clinical intervention (2009) Expert. Rev. Dermatol., 4, pp. 67-78 Lawrence, M.G., Margaryan, N.V., Loessner, D., Collins, A., Kerr, K.M., Turner, M., Seftor, E.A., Postovit, L.M., Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells (2011) Prostate, 71, pp. 1198-1209 Quail, D.F., Siegers, G.M., Jewer, M., Postovit, L.M., Nodal signalling in embryogenesis and tumorigenesis (2013) Int. J. Biochem. Cell Biol., 45, pp. 885-898 Topczewska, J.M., Postovit, L.M., Margaryan, N.V., Sam, A., Hess, A.R., Wheaton, W.W., Nickoloff, B.J., Hendrix, M.J., Embryonic and tumorigenic pathways converge via Nodal signaling: Role in melanoma aggressiveness (2006) Nat. Med, 12, pp. 925-932 Seftor, E.A., Seftor, R.E., Weldon, D.S., Kirsammer, G.T., Margaryan, N.V., Gilgur, A., Hendrix, M.J., Melanoma tumor cell heterogeneity: A molecular approach to study subpopulations expressing the embryonic morphogen nodal (2014) Semin. Oncol, 41, pp. 259-266 Hardy, K.M., Strizzi, L., Margaryan, N.V., Gupta, K., Murphy, G.F., Scolyer, R.A., Hendrix, M.J., Targeting nodal in conjunction with dacarbazine induces synergistic anticancer effects in metastatic melanoma (2015) Mol. 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Gov'T, }, affiliation={Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Universita degli Studi di Napoli "Federico II", Naples 80134, Italy. annalia.foca@gmail.com., Department of Pharmacy, Universita degli Studi di Napoli "Federico II", Naples 80131, Italy. annalia.foca@gmail.com., Bioker Multimedica, Naples 80131, Italy. Luca.Sanguigno@multimedica.it., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Universita degli Studi di Napoli "Federico II", Naples 80134, Italy. giuseppina.foca@gmail.com., Department of Pharmacy, Universita degli Studi di Napoli "Federico II", Naples 80131, Italy. giuseppina.foca@gmail.com., Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. LStrizzi@luriechildrens.org., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Universita degli Studi di Napoli "Federico II", Naples 80134, Italy. robertaiannitti@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Universita degli Studi di Napoli "Federico II", Naples 80134, Italy. rosanna.palumbo@cnr.it., Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. m-hendrix@northwestern.edu., Department of Molecular Medicine and Medical Biotechnologies, Universita degli Studi di Napoli "Federico II", Naples 80131, Italy. leonardi@unina.it., Ins}, ibbaffiliation={1}, } @article{IBB_ID_9806, author={Doti N, Scognamiglio PL, Madonna S, Scarponi C, Ruvo M, Perretta G, Albanesi C, Marasco D}, title={New mimetic peptides of the kinase-inhibitory region (KIR) of SOCS1 through focused peptide libraries}, date={2012 Apr 1}, journal={Biochemical Journal}, year={2012}, fullvolume={805}, volume={805}, pages={231--240}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84858326728&partnerID=40&md5=faa27d1fb46c92fdd0ce041ebc1b452d}, abstract={SOCS (suppressor of cytokine signalling) proteins are negative-feedback regulators of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway. Their expression levels are low under physiological conditions, but they are up-regulated in response to cytokine stimulation in many immune and inflammatory processes. Overexpression of SOCS I in keratinocyte clones abrogates the IFN gamma (interferon gamma)-induced expression of many pro-inflammatory genes and the release of related chemokines by blocking the JAK/STAT pathway. SOCS1 inhibits JAK2 kinase activity by binding the catalytic site of JAK2, with its KIR (kinase-inhibitory region) acting as a pseudo-substrate of the enzyme. In the present study, we screened a focused combinatorial peptide library of KIR to identify new peptides able to mimic its function with an improved affinity towards the JAK2 catalytic site. Using an alanine-scanning method, KIR residues that are crucial for the interaction with JAK2 were unveiled. In this way, the KIR sequence was restricted to a shorter segment and 'non-essential' residues were replaced by different amino acids following a simplified combinatorial approach. We selected a new unnatural sequence able to bind to JAK2 with K-d values in the nanomolar range. This peptide was tested in human keratinocyte cultures and reduced the phosphorylation of STAT1 and the expression levels of IRF-1 (interferon regulatory factor-1).}, keywords={Janus Kinase Signal Transducer And Activator Of Transcription Pathway (jak Stat Pathway), Kinase Inhibitory Region (kir), Mimetic Peptide, Peptide Library, Suppressor Of Cytokine Signalling 1 (socs1), Gamma Interferon, Interferon Regulatory Factor 1, Stat1 Protein, Suppressor Of Cytokine Signaling 1, Amino Acid Sequence, Article, Binding Affinity, Catalysis, Controlled Study, Enzyme Activation, Enzyme Activity, Enzyme Stability, Human, Human Cell, Keratinocyte, Normal Human, Priority Journal, Protein Analysis, Protein Binding, Protein Function, Protein Interaction, Protein Phosphorylation, Protein Structure, Protein Synthesis, Signal Transduction, Competitive, Catalytic Domain, Cultured, Circular Dichroism, Drug Evaluation, Preclinical, Drug Stability, Models, Molecular, Molecular Sequence Data, Secondary, Tertiary, Stat1 Transcription Factor, Suppressor Of Cytokine Signaling Proteins, }, references={Ihle, J.N., Witthuhn, B.A., Quelle, F.W., Yamamoto, K., Silvennoinen, O., Signaling through the hematopoietic cytokine receptors (1995) Annu. 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D., De Korte, J., Effects of etanercept on quality of life, fatigue, and depression in psoriasis (2006) Lancet, 367 (9504), pp. 6-7. , DOI 10. 1016/S0140-6736 (05) 67818-X, PII S014067360567818X Babon, J. J., Sabo, J. K., Zhang, J. G., Nicola, N. A., Norton, R. S., The SOCS box encodes a hierarchy of affinities for Cullin5: Implications for ubiquitin ligase formation and cytokine signalling suppression (2009) J. Mol. Biol., 387, pp. 162-174}, document_type={Journal Article, }, affiliation={Institute of Biostructures and Bioimaging - IBB-CNR, Via Mezzocannone 16, 80134, Naples, Italy Laboratory of Experimental Immunology, Istituto Dermopatico dell'Immacolata, Via Monti di Creta 104, 00167 Rome, Italy Department of Biological Sciences, School of Biotechnological Sciences, University Federico II, Via Mezzocannone 16, 80134, Naples, Italy}, ibbaffiliation={1}, } @article{IBB_ID_10961, author={Fassina G, Ruvo M, Palombo G, Verdoliva A, Marino M}, title={Novel ligands for the affinity-chromatographic purification of antibodies}, date={2001 Oct 30}, journal={J Biochem Biophys Methods (ISSN: 0165-022x, 0165-022xlinking)}, year={2001}, fullvolume={1155}, volume={1155}, pages={481--490}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035975879&partnerID=40&md5=a6c805aafb8beb9894e64070740335ca}, abstract={Affinity chromatography represents one of the most powerful fractionation techniques for the large-scale purification of biotechnological products. Despite its potential, the use of this methodology is limited by the availability of specific ligands for each target. Combinatorial chemistry and molecular modeling, often combined, have become interesting and innovative methods for generating novel ligands, tailored to specific biotechnological needs. One of the greatest area of application has been the discovery of novel ligands for the purification of antibodies, which represent an emerging but very important class of innovative therapeutic agents for the treatment of a vast array of diseases. Naturally available affinity ligands, such as Protein A or G for IgG purification or lectins for IgA and IgM purification, which are obtained from microorganisms or genetically modified bacteria through complex and expensive procedures, are not well suited for large-scale purification and require moreover time-consuming analytical controls to check for the presence of contaminants which may affect the safety of the purified antibody for clinical purposes. Recent results suggest that the application of combinatorial technologies and molecular modeling for the discovery of synthetic ligands may open new avenues for the development of more efficient, less expensive and - more importantly - safer procedures for antibody purification at the industrial level. © 2001 Elsevier Science B.V. All rights reserved.}, keywords={Affinity Chromatography, Antibodies, Combinatorial Chemistry, Molecular Design, Synthetic Ligands, Immunoglobulin, Lectin, Protein, Tg 19318, Unclassified Drug, Bioavailability, Biosynthesis, Biotechnology, Diagnostic Procedure, Dna Modification, Methodology, Microorganism, Molecular Model, Priority Journal, Protein Purification, Protein Targeting, Review, Technique, Combinatorial Chemistry Techniques, Peptide Library, Staphylococcal Protein A, Isolation, }, references={Fuglistaller, P., Comparison of immunoglobulin binding capacities and ligand leakage using eight different protein A affinity chromatography matrices (1989) J Immunol Methods, 124, pp. 171-17 Michetti, P., Mahan, M.J., Slauch, J.M., Mekelanos, J.J., Neutra, M.R., Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium (1992) Infect Immun, 60, pp. 1786-1792 Phalipon, A., Kaufmann, M., Michetti, P., Cavaillon, J.M., Huerre, M., Sansonetti, P., Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis (1995) J Exp Med, 182, pp. 769-778 Apter, F.M., Lencer, W.I., Finkelstein, R.A., Mekalanos, J.J., Neutra, M.R., Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro (1993) Infect Immun, 61, pp. 5271-5278 Weltzin, R., Hsu, S.A., Mittler, E.S., Georgakopoulos, K., Monath, T.P., Intranasal monoclonal immunoglobulin A against respiratory syncytial virus protects against upper and lower respiratory tract infections in mice (1994) Antimicrob Agents Chemother, 38, pp. 2785-2791 Waldam, R.H., Mach, J.P., Stella, M.M., Rowe, D.S., Secretory IgA in human serum (1970) J Immunol, 105, pp. 43-47 Khayam-Bashi, H., Blanken, R.M., Schwartz, C.L., Chromatographic separation and purification of secretory IgA from human milk (1977) Prep Biochem, 7, pp. 225-229 Roque-Barreira, M.R., Campos-Nieto, A., Jacalin: An IgA-binding lectin (1985) J Biol Chem, 134, pp. 1740-1743 Kondoh, H., Kobayashi, K., Hagiwara, K., A simple procedure for the isolation of human secretory IgA of IgA1 and IgA2 subclass by a jackfruit lectin, jacalin, affinity chromatography (1987) Mol Immunol, 24, pp. 1219-1222 Bunn-Moreno, M.M., Campos-Neto, A., Lectin(s) extracted from seeds of artocarpus integrifolia (jackfruit): Potent and selective stimulator(s) of distinct human T and B cell functions (1981) J Immunol, 127, pp. 427-430 Nagy, E., Berczi, I., Sehon, A.H., Growth inhibition of murine mammary carcinoma by monoclonal IgE antibodies specific for the mammary tumor virus (1991) Cancer Immunol Immunother, 34, pp. 63-69 Phillips, T.M., More, N.S., Queen, W.D., Thompson, A.M., Isolation and quantitation of serum IgE levels by high-performance immunoaffinity chromatography (1985) J Chromatogr, 327, pp. 205-211 Lehrer, S.B., Isolation of IgE from normal mouse serum (1979) Immunology, 36, pp. 103-109 Ikeyama, S., Nakagawa, S., Arakawa, M., Sugino, H., Kakinuma, A., Purification and characterization of IgE produced by human myeloma cell line, U266 (1986) Mol Immunol, 23, pp. 159-167 Quadri, S.M., Malik, A.B., Tang, X.Z., Patenia, R., Freedman, R.S., Vriesendorp, H.M., Preclinical analysis of intraperitoneal administration of 111In-labeled human tumor reactive monoclonal IgM AC63-2B12 (1995) Cancer Res, 55, pp. 5736-5742 Nevens, J.R., Mallia, A.K., Wendt, M.W., Smith, P.K., Affinity chromatographic purification of immunoglobulin M antibodies utilizing immobilized mannan binding protein (1992) J Chromatogr, 597, pp. 247-253 Polson, A., Von Wechmar, M.B., Van Regenmortel, M.H.V., Isolation of viral IgY antibodies from egg yolks of immunized hens (1980) Immunol Commun, 9, pp. 475-493 Jensenius, J.C., Anderson, I., Hau, J., Crove, M., Koch, C., Eggs: Conveniently packaged antibodies. 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Leiden: ESCOM Marino, M., Campanile, N., Ippolito, A., Scarallo, A., Ruvo, M., Fassina, G., Structurally constrained selective ligands for mouse immunoglobulins (1999) Peptides 98, pp. 776-777. , Bajusz S, Hudecz F, editors. Budapest: Academia Kiado Li, R., Dowd, V., Steward, D.J., Burton, S.J., Lowe, C.R., Design, synthesis, and application of a protein A mimetic (1998) Nat Biotechnol, 16, pp. 190-195 Apter, F. M., Lencer, W. I., Finkelstein, R. A., Mekalanos, J. J., Neutra, M. R., Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro (1993) Infect Immun, 61, pp. 5271-5278 Waldam, R. H., Mach, J. P., Stella, M. M., Rowe, D. S., Secretory IgA in human serum (1970) J Immunol, 105, pp. 43-47 Roque-Barreira, M. R., Campos-Nieto, A., Jacalin: An IgA-binding lectin (1985) J Biol Chem, 134, pp. 1740-1743 Bunn-Moreno, M. M., Campos-Neto, A., Lectin (s) extracted from seeds of artocarpus integrifolia (jackfruit): Potent and selective stimulator (s) of distinct human T and B cell functions (1981) J Immunol, 127, pp. 427-430 Phillips, T. M., More, N. S., Queen, W. D., Thompson, A. M., Isolation and quantitation of serum IgE levels by high-performance immunoaffinity chromatography (1985) J Chromatogr, 327, pp. 205-211 Lehrer, S. B., Isolation of IgE from normal mouse serum (1979) Immunology, 36, pp. 103-109 Quadri, S. M., Malik, A. B., Tang, X. Z., Patenia, R., Freedman, R. S., Vriesendorp, H. M., Preclinical analysis of intraperitoneal administration of 111In-labeled human tumor reactive monoclonal IgM AC63-2B12 (1995) Cancer Res, 55, pp. 5736-5742 Nevens, J. R., Mallia, A. K., Wendt, M. W., Smith, P. K., Affinity chromatographic purification of immunoglobulin M antibodies utilizing immobilized mannan binding protein (1992) J Chromatogr, 597, pp. 247-253 Jensenius, J. C., Anderson, I., Hau, J., Crove, M., Koch, C., Eggs: Conveniently packaged antibodies. Methods for purification of yolk IgG (1981) J Immunol Methods, 46, pp. 63-68 Carrol, S. B., Stollar, B. D., Antibodies to calf thymus RNA polymerase II from egg yolks of immunized hens (1983) J Biol Chem, 258, pp. 24-26 Akita, E. M., Nakai, S., Comparison of four purification methods for the production of immunoglobulins from eggs laid by hens immunized with an enteroxigenic E. coli strain (1993) J Immunol Methods, 160, pp. 207-214 Song, C. -S., Yu, J. -H., Bai, D. H., Hester, P. Y., Kim, K. -H., Antibodies to a-subunit of insulin receptor from eggs of immunized hens (1985) J Immunol, 135, pp. 3354-3360 Larsson, A., Sj quist, J., Chicken antibodies: A tool to avoid false positive results by rheumatoid factor in latex fixation tests (1988) J Immunol Methods, 108, pp. 205-208 Hassl, A., Asp ck, H., Purification of egg yolk immunoglobulins. A two-step procedure using hydrophobic interaction chromatography and gel filtration (1988) J Immunol Methods, 110, pp. 225-228 Ngo, T. T., Khatter, N., Chemistry and preparation of affinity ligands useful in immunoglobulin isolation and serum-protein separation (1990) J Chromatogr, 510, pp. 281-291 Houghten, R. A., Pinilla, C., Blondelle, S. E., Appel, J. R., Dooley, C. T., Cuervo, J. H., Generation and use of synthetic peptide combinatorial libraries for basic research and discovery (1991) Nature, 354, pp. 84-86 Lam, K. S., Salmon, S. E., Hersh, E. M., Hruby, V. J., Kazmiersky, W. M., Knapp, R. J., A new type of synthetic peptide library for identifying ligand-binding activity (1991) Nature, 354, pp. 82-84 Tam, J. P., Synthetic peptide vaccine design: Synthesis and properties of a high-density multiple antigenic peptide system (1988) Proc Natl Acad Sci U S A, 85, pp. 5409-5413}, document_type={Journal Article, Review, }, affiliation={Biopharmaceuticals, TECNOGEN, Parco Scientifico, 81015 Piana di Monte Verna (CE), Italy}, ibbaffiliation={1}, } @article{IBB_ID_9701, author={Marino M, Rossi M, Ruvo M, Fassina G}, title={Novel molecular targets for systemic lupus erythematosus}, date={2002 Jun}, journal={Curr Drug Targets (ISSN: 1389-4501)}, year={2002}, fullvolume={345}, volume={345}, pages={223--228}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036001051&partnerID=40&md5=f20fb6aa35c6d58abf643f305ae56dcf}, abstract={For a long time the complement cascade has been believed to be the predominant pathway to inflammation and tissue destruction in autoimmune diseases such as systemic lupus erythematosus. Recently, new evidences show that FcRs may share the primacy with complement cascade, playing an equal or greater role in the disease process. The generation of specific mouse strains deficient in individual components has clarified the different role played by complement and Fc receptors in their interaction with ICs, illustrating that complement is essential for innate immunity against microbial pathogens, requiring natural antibodies to mediate its protective effects, whereas FcγRs have evolved as the principal system for coupling antigen-antibody complexes to effector cells and initiate the inflammatory cascade. Validation of FcRs as new therapeutic targets for autoimmune diseases, in particular for Systemic Lupus Erythematosus (SLE), has been provided by a large number of studies where the biological action of soluble forms of FcγRs or of monoclonal antibodies targeting Fc receptors has been assessed. Additional support to the role of FcRs in SLE has been provided by data obtained with compounds derived from combinatorial chemistry, such as TG19320, a tetrameric tripeptide which interferes with IgG/FcγR interaction in vitro and prevents glomerulonephritis in vivo in a SLE susceptible mouse strain. These findings might open the way to new therapeutic approaches for disorders where the role of FcRs has been established, including not only autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis, multiple myeloma, but also acquired immunodeficiency syndrome (AIDS).}, keywords={Antiidiotypic Antibody, Antiinflammatory Agent, Antimalarial Agent, Azathioprine, Cd16 Antigen, Chymotrypsin, Complement, Corticosteroid, Cyclophosphamide, Cyclosporin, Fc Receptor, Glucocorticoid, Immunoglobulin G, Immunosuppressive Agent, Methotrexate, Monoclonal Antibody, Pepsin A, Tetramer, Tg 19320, Tripeptide Derivative, Unclassified Drug, Oligopeptide, Acquired Immune Deficiency Syndrome, Animal Experiment, Animal Model, Antigen Antibody Complex, Autoimmune Disease, Cataract, Combinatorial Chemistry, Controlled Study, Depression, Disease Predisposition, Drug Bioavailability, Drug Blood Level, Drug Efficacy, Drug Formulation, Drug Half Life, Drug Mechanism, Drug Stability, Drug Synthesis, Drug Targeting, Drug Urine Level, Effector Cell, Female, Glomerulonephritis, Human, In Vivo Study, Infection, Inflammation, Insomnia, Kidney Injury, Microbial Immunity, Molecular Interaction, Mouse, Mouse Strain, Multiple Myeloma, Nausea And Vomiting, Nonhuman, Osteoporosis, Pathogenesis, Review, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Tissue Injury, Validation Process, Weight Gain, Metabolism, Pathophysiology, }, references={Mannik, M., (1982) Arthritis Rheum, 25, pp. 783-78 Mannik, M., Agodoa, L.Y., David, K.A., (1983) J. 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H., Ebling, F. M., (1984) J. Immunol, 132, pp. 187-190 Sylvestre, D. L., Ravetch, J. V., (1994) Science, 265, pp. 1095-1098 Hoover, R. G., Lary, C., Page, R., Travis, P., Owens, R., Flick, J., Kornbluth, J., Barlogie, B., (1995) J. Clin. Invest, 95, pp. 241-247 Bich-Thuy, L. T., Samarut, C., Brochier, J., Revillard, J. P., (1981) J. Immunol, 127, pp. 1299-1303 van de Winkel, J. G. J., Capel, P. J. A., (1996) Human IgG Fc Receptors, , (eds.) R. G. Landes Company}, document_type={Journal Article, }, affiliation={XEPTAGEN S.p.A, Via A. Olivetti 1, Pozzuoli NA, Italy XEPTAGEN S. p. A, Via A. Olivetti 1, Pozzuoli NA, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53791, author={Giaquinto M, Micco A, Aliberti A, Bobeico E, La Ferrara V, Ruvo M, Ricciardi A, Cusano A}, title={Optimization Strategies for Responsivity Control of Microgel Assisted Lab-On-Fiber Optrodes}, date={2018 Apr 6}, journal={Sensors (ISSN: 1424-8220linking, 1424-3210, 1424-8220electronic)}, year={2018}, fullvolume={213}, volume={213}, pages={N/D--N/D}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045105251&doi=10.3390%2fs18041119&partnerID=40&md5=d89e2e1a230b598702e641f42f61c836}, abstract={Integrating multi-responsive polymers such as microgels onto optical fiber tips, in a controlled fashion, enables unprecedented functionalities to Lab-on-fiber optrodes. The creation of a uniform microgel monolayer with a specific coverage factor is crucial for enhancing the probes responsivity to a pre-defined target parameter. Here we report a reliable fabrication strategy, based on the dip coating technique, for the controlled realization of microgel monolayer onto unconventional substrates, such as the optical fiber tip. The latter was previously covered by a plasmonic nanostructure to make it sensitive to superficial environment changes. Microgels have been prepared using specific Poly( N -isopropylacrylamide)-based monomers that enable bulky size changes in response to both temperature and pH variations. The formation of the microgel monolayer is efficiently controlled through the selection of suitable operating pH, temperature and concentration of particle dispersions used during the dipping procedure. The effect of each parameter has been evaluated, and the validity of our procedure is confirmed by means of both morphological and optical characterizations. We demonstrate that when the coverage factor exceeds 90%, the probe responsivity to microgels swelling/collapsing is significantly improved. Our study opens new paradigms for the development of engineered microgels assisted Lab-on-Fiber probes for biochemical applications.}, keywords={Biochemical Sensing, Lab-On-Fiber, Microgels, Smart Polymers, Acrylic Monomers, Laboratories, Monolayers, Optical Fibers, Plasmonics, Probes, Substrates, Bio-Chemical Applications, Dip Coating Techniques, Micro-Gels, Optical Characterization, Plasmonic Nanostructures, Poly (n Isopropylacrylamide), Optical Fiber Fabrication, }, references={Vaiano, P., Carotenuto, B., Pisco, M., Ricciardi, A., Quero, G., Consales, M., Crescitelli, A., Cusano, A., Lab on fiber technology for biological sensing applications (2016) Laser Photonics Rev, 10, pp. 922-96 Cusano, A., Consales, M., Crescitelli, A., Ricciardi, A., (2015) Lab-On-Fiber Technology, 56. , Springer: Berlin, Germany Consales, M., Ricciardi, A., Crescitelli, A., Esposito, E., Cutolo, A., Cusano, A., Lab-on-fiber technology: Toward multifunctional optical nanoprobes (2012) ACS Nano, 6, pp. 3163-3170 Ricciardi, A., Consoles, M., Quero, G., Crescitelli, A., Esposito, E., Cusano, A., Versatile optical fiber nanoprobes: From plasmonic biosensors to polarization-sensitive devices (2014) ACS Photonics, 1, pp. 69-78 Ricciardi, A., Aliberti, A., Giaquinto, M., Micco, A., Cusano, A., Microgel Photonics: A Breathing Cavity onto Optical Fiber Tip (2015) Proceedings of the 24Th International Conference on Optical Fibre Sensors, , Curitiba, Brazil, 28 September–2 October 2015 SPIE: Bellingham, WA, USA Kostovski, G., Stoddart, P.R., Mitchell, A., The optical fiber tip: An inherently light-coupled microscopic platform for micro-and nanotechnologies (2014) Adv. Mater., 26, pp. 3798-3820 Pelton, R., Hoare, T., Microgels and their synthesis: An introduction (2011) Microgel Suspensions: Fundamentals and Applications, 1, pp. 1-32. , John Wiley & Sons: Hoboken, NJ, USA Plamper, F.A., Richtering, W., Functional microgels and microgel systems (2017) Accounts Chem. Res., 50, pp. 131-140 Wei, M.L., Gao, Y.F., Li, X., Serpe, M.J., Stimuli-responsive polymers and their applications (2017) Polym. Chem., 8, pp. 127-143 Aliberti, A., Ricciardi, A., Giaquinto, M., Micco, A., Bobeico, E., la Ferrara, V., Ruvo, M., Cusano, A., Microgel assisted lab-on-fiber optrode (2017) Sci. Rep., 7, p. 14459 Giaquinto, M., Ricciardi, A., Aliberti, A., Micco, A., Bobeico, E., Ruvo, M., Cusano, A., Light-microgel interaction in resonant nanostructures (2018) Sci. Rep., , under review Jiang, Y., Chen, J., Deng, C., Suuronen, E.J., Zhong, Z., Click hydrogels, microgels and nanogels: Emerging platforms for drug delivery and tissue engineering (2014) Biomaterials, 35, pp. 4969-4985 Oh, J.K., Drumright, R., Siegwart, D.J., Matyjaszewski, K., The development of microgels/nanogels for drug delivery applications (2008) Prog. Polym. Sci., 33, pp. 448-477 Schmidt, S., Zeiser, M., Hellweg, T., Duschl, C., Fery, A., Möhwald, H., Adhesion and mechanical properties of pnipam microgel films and their potential use as switchable cell culture substrates (2010) Adv. Funct. Mater., 20, pp. 3235-3243 Islam, M.R., Ahiabu, A., Li, X., Serpe, M.J., Poly (N-isopropylacrylamide) microgel-based optical devices for sensing and biosensing (2014) Sensors, 14, pp. 8984-8995 Nerapusri, V., Keddie, J.L., Vincent, B., Bushnak, I.A., Swelling and deswelling of adsorbed microgel monolayers triggered by changes in temperature, pH, and electrolyte concentration (2006) Langmuir, 22, pp. 5036-5041 Serpe, M.J., Jones, C.D., Lyon, L.A., Layer-by-layer deposition of thermoresponsive microgel thin films (2003) Langmuir, 19, pp. 8759-8764 Schmidt, S., Motschmann, H., Hellweg, T., von Klitzing, R., Thermoresponsive surfaces by spin-coating of PNIPAM-co-PAA microgels: A combined AFM and ellipsometry study (2008) Polymer, 49, pp. 749-756 Sorrell, C.D., Lyon, L.A., Deformation controlled assembly of binary microgel thin films (2008) Langmuir, 24, pp. 7216-7222 Schmidt, S., Hellweg, T., von Klitzing, R., Packing density control in P (NIPAM-co-AAc) microgel monolayers: Effect of surface charge, pH, and preparation technique (2008) Langmuir, 24, pp. 12595-12602 Tsuji, S., Kawaguchi, H., Colored thin films prepared from hydrogel microspheres (2005) Langmuir, 21, pp. 8439-8442 Sakai, T., Takeoka, Y., Seki, T., Yoshida, R., Organized monolayer of thermosensitive microgel beads prepared by double-template polymerization (2007) Langmuir, 23, pp. 8651-8654 South, A.B., Whitmire, R.E., Garcia, A.J., Lyon, L.A., Centrifugal deposition of microgels for the rapid assembly of nonfouling thin films (2009) ACS Appl. Mater. Interfaces, 1, pp. 2747-2754 Singh, N., Bridges, A.W., García, A.J., Lyon, L.A., Covalent tethering of functional microgel films onto poly (Ethylene terephthalate) surfaces (2007) Biomacromolecules, 8, pp. 3271-3275 Meng, Z., Cho, J.K., Debord, S., Breedveld, V., Lyon, L.A., Crystallization behavior of soft, attractive microgels (2007) J. Phys. Chem. B, 111, pp. 6992-6997 Sorrell, C.D., Carter, M.C., Serpe, M.J., A “paint-on” protocol for the facile assembly of uniform microgel coatings for color tunable etalon fabrication (2011) ACS Appl. Mater. Interfaces, 3, pp. 1140-1147 Hu, L., Serpe, M.J., The influence of deposition solution pH and ionic strength on the quality of poly (N-isopropylacrylamide) microgel-based thin films and etalons (2013) ACS Appl. Mater. Interfaces, 5, pp. 11977-11983 Islam, M.R., Irvine, J., Serpe, M.J., Photothermally induced optical property changes of poly (N-isopropylacrylamide) microgel-based etalons (2015) ACS Appl. Mater. Interfaces, 7, pp. 24370-24376 Sorrell, C.D., Serpe, M.J., Reflection order selectivity of color-tunable poly(N-isopropylacrylamide) microgel based etalons (2011) Adv. Mater., 23, pp. 4088-4092 Lu, Y., Drechsler, M., Charge-induced self-assembly of 2-dimensional thermosensitive microgel particle patterns (2009) Langmuir, 25, pp. 13100-13105 Iori, F., Corni, S., Di Felice, R., Unraveling the interaction between histidine side chain and the Au(111) surface: A DFT study (2008) J. Phys. Chem. C, 112, pp. 13540-13545 Yin, X., Hoffman, A.S., Stayton, P.S., Poly (N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH (2006) Biomacromolecules, 7, pp. 1381-1385 Wang, B., Xu, X.-D., Wang, Z.-C., Cheng, S.-X., Zhang, X.-Z., Zhuo, R.-X., Synthesis and properties of pH and temperature sensitive P (NIPAAm-co-DMAEMA) hydrogels (2008) Colloids Surf. B Biointerfaces, 64, pp. 34-41 Aguilar, M., San Román, J., Introduction to smart polymers and their applications (2014) Smart Polymers and Their Applications, pp. 1-11. , Elsevier: New York, NY, USA}, document_type={Journal Article, }, affiliation={Optoelectronics Group, Department of Engineering, University of Sannio, I-82100 Benevento, Italy. martino.giaquinto@unisannio.it. ENEA, Portici Research Center, P. le E. Fermi 1, Portici, I-80055 Napoli, Italy. eugenia.bobeico@enea.it. Institute of Biostructure and Bioimaging, National Research Council, I-80143 Napoli, Italy. menotti.ruvo@unina.it.}, ibbaffiliation={1}, } @article{IBB_ID_9055, author={Doti N, Marasco D, Pedone C, Sabatella M, Ruvo M}, title={Optimizing A Kinase Assay For Ikkbeta On An Hts Station}, date={2009 Dec}, journal={J Biomol Screen (ISSN: 1087-0571, 1552-454x, 1552-454xelectronic)}, year={2009}, fullvolume={302}, volume={302}, pages={1263--1268}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-71949123743&partnerID=40&md5=1ca3dd845d14830ede439b2982d74d8b}, abstract={Using a commercially available time-resolved fluorescence resonance energy transfer (TR-FRET)-based assay for IKKβ, the authors have automated the assay procedure on a high-throughput screening station to carry out screening campaigns on multiwell plates. They have determined the Z′ factor and optimized volumes, times, and time-resolved fluorescence parameters. They have also compared 2 kinases with different fusion tags, the influence of different enzyme/substrate ratios and of DMSO presence at different concentration. The authors found that glutathione S-transferase (GST)-fused IKKβ shows better signal-to-noise (S/N) ratios over the poly-histidine-tagged variant. The substrate can be used at 50 nM with optimal performances when the enzyme is used at 2 nM. DMSO at 0.2% and 1% only slightly affects the S/N ratio, whereas when used at 2%, the final concentration deriving from a 50-fold dilution from a 5-mM stock solution in pure solvent, S/N undergoes a decrease of about 15%. Under the optimized conditions, the assay Z′ factor calculated over 192 data points has an optimized value of 0.881 and allows the testing of 94 molecules in quadruplicate in 140 min. © 2009 Society for Biomolecular Sciences.}, keywords={Hts, Ikkβ, Tr-Fret, Z′ Factor, Dimethyl Sulfoxide, Glutathione Transferase, Histidine, I Kappa B Kinase Beta, I Kappa B Kinase Inhibitor, Article, Controlled Study, Enzyme Activity, Enzyme Assay, Fluorescence Resonance Energy Transfer, High Throughput Screening, Priority Journal, High-Throughput Screening Assays, I-Kappa B Kinase, I-Kappa B Proteins, Time Factors, Z Factor, Methods, Metabolism, }, references={Strnad, J., Burke, J.R., IkappaB kinase inhibitors for treating autoimmune and inflammatory disorders: Potential and challenges (2007) Trends Pharmacol Sci, 28, pp. 142-14 Goldstein, D.M., Gray, N.S., Zarrinkar, P.P., High-throughput kinase profiling as a platform for drug discovery (2008) Nat Rev Drug Discov, 7, pp. 391-397 Oliver Von Ahsen, U.B., High-throughput screening for kinase inhibitors (2005) ChemBioChem, 6, pp. 481-490 Sera, T., Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors (2007) Tanpakushitsu Kakusan Koso, 52 (SUPPL.), pp. 1812-1813 Thaimattam, R., Banerjee, R., Miglani, R., Iqbal, J., Protein kinase inhibitors: Structural insights into selectivity (2007) Curr Pharm des, 13, pp. 2751-2765 Klumpp, M., Boettcher, A., Becker, D., Meder, G., Blank, J., Leder, L., Readout technologies for highly miniaturized kinase assays applicable to high-throughput screening in a 1536-well format (2006) J Biomol Screen, 11, pp. 617-633 Xu, Q.H., Wang, S., Korystov, D., Mikhailovsky, A., Bazan, G.C., Moses, D., The fluorescence resonance energy transfer (FRET) gate: A time-resolved study (2005) Proc Natl Acad Sci USA, 102, pp. 530-535 Moshinsky, D.J., Ruslim, L., Blake, R.A., Tang, F., Widely applicable, high-throughput TR-FRET assay for the measurement of kinase autophosphorylation: VEGFR-2 as a prototype (2003) J Biomol Screen, 8, pp. 447-452 Bazin, H., Trinquet, E., Mathis, G., Time resolved amplification of cryptate emission: A versatile technology to trace biomolecular interactions (2002) J Biotechnol, 82, pp. 233-250 Lance Ultra IKKβ Kinase Assay, , www.perkinelmer.com, Technical note U-TRF. Waltham, MA: PerkinElmer Zhang, J.H., Chung, T.D., Oldenburg, K.R., A simple statistical parameter for use in evaluation and validation of high throughput screening assays (1999) J Biomol Screen, 4, pp. 67-73 Podolin, P.L., Callahan, J.F., Bolognese, B.J., Li, Y.H., Carlson, K., Davis, T.G., Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of Iκb kinase 2, TPCA-1 (2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell proliferation (2005) J Pharmacol Exp Ther, 312, pp. 373-381 Goldstein, D. M., Gray, N. S., Zarrinkar, P. P., High-throughput kinase profiling as a platform for drug discovery (2008) Nat Rev Drug Discov, 7, pp. 391-397 Xu, Q. H., Wang, S., Korystov, D., Mikhailovsky, A., Bazan, G. C., Moses, D., The fluorescence resonance energy transfer (FRET) gate: A time-resolved study (2005) Proc Natl Acad Sci USA, 102, pp. 530-535 Moshinsky, D. J., Ruslim, L., Blake, R. A., Tang, F., Widely applicable, high-throughput TR-FRET assay for the measurement of kinase autophosphorylation: VEGFR-2 as a prototype (2003) J Biomol Screen, 8, pp. 447-452 Lance Ultra IKK Kinase Assay, , www. perkinelmer. com, Technical note U-TRF. Waltham, MA: PerkinElmer Zhang, J. H., Chung, T. D., Oldenburg, K. R., A simple statistical parameter for use in evaluation and validation of high throughput screening assays (1999) J Biomol Screen, 4, pp. 67-73 Podolin, P. L., Callahan, J. F., Bolognese, B. J., Li, Y. H., Carlson, K., Davis, T. G., Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of I b kinase 2, TPCA-1 (2- [(aminocarbonyl) amino] -5- (4-fluorophenyl) -3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell proliferation (2005) J Pharmacol Exp Ther, 312, pp. 373-381}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone, 16, 80134, Napoli, Italy Dipartimento Delle Scienze Biologiche, Università di Napoli, Federico II, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54291, author={Tarallo V, Iaccarino E, Cicatiello V, Sanna R, Ruvo M, De Falco S}, title={Oral Delivery of a Tetrameric Tripeptide Inhibitor of VEGFR1 Suppresses Pathological Choroid Neovascularization}, date={2020 Jan 9}, journal={Int J Mol Sc (ISSN: 1422-0067linking, 1661-6596, 1422-0067electronic)}, year={2020}, fullvolume={182}, volume={182}, pages={N/D--N/D}, url={}, abstract={Age-related macular degeneration (AMD) is the primary cause of blindness in advanced countries. Repeated intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents has represented an important advancement for the therapy of wet AMD with significative results in terms of blindness prevention and partial vision restore. Nonetheless, some patients are not responsive or do not attain significant visual improvement, intravitreal injection may cause serious complications and important side effects have been reported for the prolonged block of VEGF-A. In order to evaluate new anti-angiogenic strategies, we focused our attention on VEGF receptor 1 (VEGFR1) developing a specific VEGFR-1 antagonist, a tetrameric tripeptide named inhibitor of VEGFR 1 (iVR1). We have evaluated its anti-angiogenic activity in the preclinical model of AMD, the laser-induced choroid neovascularization (CNV). iVR1 is able to potently inhibit CNV when delivered by intravitreal injection. Surprisingly, it is able to significantly reduce CNV also when delivered by gavage. Our data show that the specific block of VEGFR1 in vivo represents a valid alternative to the block of VEGF-A and that the inhibition of the pathological neovascularization at ocular level is also possible by systemic delivery of compounds not targeting VEGF-A.}, keywords={Amd , Cnv , Vegfr1 , Multimeric Peptides , Oral Delivery, Administration, Animals , Choroidal Neovascularization Drug Therapy Pathology , Intravitreal Injections , Lasers , Inbred C57bl , Oligopeptides Administration, Dosage Chemistry Therapeutic Use , Spectroscopy, Fourier Transform Infrared , Trifluoroacetic Acid Chemistry , Vascular Endothelial Growth Factor Receptor-1 Antagonists, Inhibitors Metabolism, }, references={}, document_type={Journal Article, }, affiliation={Istituto di Genetica e Biofisica 'Adriano Buzzati-Traverso'-CNR, 80131 Napoli, Italy. Istituto di Biostrutture e Bioimmagini-CNR, 80134 Napoli, Italy. BIOVIIIx s.r.l., Department of R&D, 80142 Napoli, Italy. ANBITION s.r.l., Department of R&D, 80128 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_54820, author={Sandomenico A, Gogliettino M, Iaccarino E, Fusco C, Caporale A, Ruvo M, Palmieri G, Cocca E}, title={Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme}, date={2021 Dec 31}, journal={Int J Mol Sci (ISSN: 1422-0067electronic)}, year={2021}, fullvolume={3}, volume={3}, pages={N/D--N/D}, url={}, abstract={APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48–64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.}, keywords={}, references={}, document_type={Journal Article}, affiliation={Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), 80134 Napoli, Italy annamaria.sandomenico@cnr.it (A.S.) emanuela.iaccarino@gmail.com (E.I.) andrea.caporale@cnr.it (A.C.) Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), 80131 Napoli, Italy marta.gogliettino@ibbr.cnr.it (M.G.) carmela.fusco@ibbr.cnr.it (C.F.) ennio.cocca@ibbr.cnr.it (E.C.)}, ibbaffiliation={1}, } @article{IBB_ID_9199, author={Marasco D, Perretta G, Sabatella M, Ruvo M}, title={Past and Future Perspectives of Synthetic Peptide Libraries}, date={2008 Oct}, journal={Curr Protein Pept Sci (ISSN: 1389-2037, 1389-2037linking)}, year={2008}, fullvolume={508}, volume={508}, pages={447--467}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-55949103501&partnerID=40&md5=15ce760cecfb8ea8831e37c94aeca539}, abstract={Combinatorial preparation and HTS of arrays of compounds have increased the speed of drug discovery. A strong impulse in this field has come by the introduction of the solid phase synthesis method that, through automation and miniaturization, has paved the way to the preparation of large collections of compounds in compact and trackable formats. Due to the well established synthetic procedures, peptides have been largely used to develop the basic concepts of combinatorial chemistry and peptide libraries are still successfully employed in screening programs. However, peptides generally do not fulfil the requirements of low conformational flexibility, stability and bioavailability needed for good drug candidates and peptide leads with high potency and selectivity are often made "druggable" by conversion to more stable structures with improved pharmacological profiles. Such an approach makes the screening of peptide libraries still a valuable tool for drug discovery. We propose here a panoramic review of the most common methods for the preparation and screening of peptide libraries and the most interesting findings of the last decade. We also report on a new approach we follow in our laboratory that is based on the use of "simplified" libraries composed by a minimum number of non-redundant amino acids for the assembly of short peptides. The choice of amino acids is dictated by diversity in lipophilicity, MW, charge and polarity. Newly identified active sequences are then modified by preparing new variants containing analogous amino acids, so that the chemical space occupied by the excluded residues can be explored. This approach offers the advantage of simplifying the synthesis and deconvolution of libraries and provides new active compounds with a molecular size similar to that of small molecules, to which they can be easily converted.}, keywords={Combinatorial Chemistry, High Throughput Screening, Molecular Complexity, Peptide Libraries, Simplified Libraries, Amino Acid, Cell Penetrating Peptide, Dendrimer, Galectin, Glycoprotein, Heparin, Hepatitis Vaccine, Human Immunodeficiency Virus Vaccine, Liposome, Nanoparticle, Peptide Deformylase, Peptide Deformylase Inhibitor, Peptide Derivative, Peptide Inhibitor, Phosphotransferase Inhibitor, Proprotein Convertase 1, Proprotein Convertase 1 Inhibitor, Proprotein Convertase 2 Inhibitor, Protein Inhibitor, Proteinase Inhibitor, Resin, Serine Proteinase, Synthetic Peptide, Tetrapeptide, Tyrosinase Inhibitor, Unclassified Drug, Affinity Chromatography, Antigenicity, Automation, Binding Affinity, Capillary Electrophoresis, Catalyst, Chemoluminescence, Drug Delivery System, Drug Design, Drug Half Life, Drug Mechanism, Drug Potency, Drug Screening, Drug Specificity, Enzyme Inhibition, Enzyme Linked Immunosorbent Assay, Fluorescence Resonance Energy Transfer, High Performance Liquid Chromatography, Ligand Binding, Lipophilicity, Mass Spectrometry, Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry, Molecular Weight, Nonhuman, Nuclear Magnetic Resonance, Peptide Synthesis, Protein Assembly, Protein Conformation, Protein Denaturation, Protein Microarray, Protein Protein Interaction, Protein Stability, Protein Structure, Protein Targeting, Review, Rna Translation, Robotics, Thermodynamics, Amino Acid Sequence, Methodology, Molecular Genetics, Combinatorial Chemistry Techniques, Molecular Sequence Data, }, references={Darvas, F., Dorman, G., Urge, L., Szabo, I., Ronai, Z., Sasvari-Szekely, M., (2001) Pure Appl. 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Biotechnol, 7 (4), p. 261}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53181, author={Selis F, Focà G, Sandomenico A, Marra C, Di Mauro C, Jotti GS, Scaramuzza S, Politano A, Sanna R, Ruvo M, Tonon G}, title={Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen}, date={2016 Apr 1}, journal={Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking)}, year={2016}, fullvolume={237}, volume={237}, pages={N/D--N/D}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962385296&doi=10.3390%2fijms17040491&partnerID=40&md5=35ef6085d9521fc0431927bb55bd407e}, abstract={ PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and stability toward proteases, however their size lowers to some extent their potential because of a reduced ability to penetrate tissues, especially those of tumor origin. Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much less well retained in circulation. We have here investigated the effects of various PEGylations on the binding properties and half-life of Fab fragments derived from the enzymatic splitting of Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects the ability to recognize the target antigen in a way that is dependent on the extent and position of the chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must be carefully considered for the design of strategies based on the use of antibody fragments. }, keywords={Fab, Pegylation, Antibody Fragment, Papain Digestion, Pepsin Digestion, Pharmacokinetics, }, references={}, document_type={Journal Article, }, affiliation={Bioker srl-Multimedica Group, c/o Institute of Genetics and Biophysics, National Research Council (CNR-IGB) via P. Castellino 111, }, ibbaffiliation={1}, } @article{IBB_ID_12379, author={Ruvo M, Marasco D, Viparelli F, Tornatore L, Sandomenico A, Doti N, Pedone C, Benedetti E, Monti SM}, title={Peptide antagonists of protein-protein interactions identified by screening protein fragments derived by enzyme degradation}, date={2008 Sep}, journal={J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print)}, year={2008}, fullvolume={317}, volume={317}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_9059, author={Viparelli F, Doti N, Monti SM, Marasco D, Dathan N, Pedone C, Miele C, Formisano P, Beguinot F, Ruvo M}, title={Peptide antagonists of the PED-hPLD1 binding}, date={2009}, journal={Adv Exp Med Biol (ISSN: 0065-2598, 0065-2598print, 0065-2598linking)}, year={2009}, fullvolume={341}, volume={341}, pages={445--446}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-66349108178&partnerID=40&md5=c6cd6424ad6504a5ac5f4a125552b0e6}, abstract={}, keywords={Peptide, Phospholipase D, Amino Acid Sequence, Animal, Article, Chemistry, Human, Metabolism, Molecular Genetics, Mouse, Protein Binding, Transgenic Mouse, Molecular Sequence Data, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini - CNR, via Mezzocannone 16, Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_9060, author={Sandomenico A, Marasco D, Monti SM, Saviano M, Pedone C, Benedetti E, Ruvo M}, title={Peptides binding the type E immunoglobulins}, date={2009}, journal={Adv Exp Med Biol (ISSN: 0065-2598, 0065-2598print)}, year={2009}, fullvolume={412}, volume={412}, pages={573--574}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-66349106864&partnerID=40&md5=49279e418c7d993790632b7e5d594bab}, abstract={}, keywords={Immunoglobulin E, Peptide, Amino Acid Sequence, Antibody Specificity, Article, Enzyme Linked Immunosorbent Assay, Metabolism, Protein Binding, Enzyme-Linked Immunosorbent Assay, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone, 16 - 80134 Napoli, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_52751, author={Cicatiello V, Apicella I, Tudisco L, Tarallo V, Formisano L, Sandomenico A, Kim Y, Bastos-Carvalho A, Orlandi A, Ambati J, Ruvo M, Bianco R, de Falco S}, title={Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models}, date={2015}, journal={Oncotarget (ISSN: 1949-2553, 1949-2553electronic, 1949-2553linking)}, year={2015}, fullvolume={380}, volume={380}, pages={10563--10576}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84929587235&partnerID=40&md5=189b1ed1e094fcd5baad005a775fbf0b}, abstract={To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was able to synergize with irinotecan determining a shrinkage of tumors that became undetectable after three weeks of combined treatment. Such treatment induced a significant prolongation of survival similar to that observed with bevacizumab and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116 cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid neovascularization after a single intravitreal injection. Collectively, data showed the strong potential of iVR1 peptide as a new anti-tumor and anti-metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as therapeutic anti-angiogenic agents in different pathological contexts.}, keywords={Angiogenesis, Choroid Neovascularization, Colorectal Cancer, Metastasis, Vegfr1, Angiogenesis Inhibitor, Bevacizumab, Inhibitor Of Vasculotropin Receptor 1, Irinotecan, Unclassified Drug, Animal Cell, Animal Experiment, Animal Model, Animal Tissue, Antiangiogenic Activity, Antineoplastic Activity, Article, Cancer Combination Chemotherapy, Cancer Inhibition, Cancer Model, Cancer Prognosis, Cancer Survival, Dose Response, Drug Activity, Drug Dose Comparison, Drug Megadose, Drug Potency, Drug Potentiation, Hct116 Cell Line, Human, Human Cell, In Vitro Study, In Vivo Study, Lung Metastasis, Macrophage, Macrophage Migration Inhibition, Metastasis Inhibition, Monocyte, Mouse, Nonhuman, Pericyte, Protein Phosphorylation, Single Drug Dose, Subretinal Neovascularization, Survival Time, Treatment Duration, Treatment Outcome, Tumor Invasion, Tumor Vascularization, }, references={Carmeliet, P., Jain, R.K., Molecular mechanisms and clinical applications of angiogenesis (2011) Nature., 473, pp. 298-30 Potente, M., Gerhardt, H., Carmeliet, P., Basic and therapeutic aspects of angiogenesis (2011) Cell., 146, pp. 873-887 Tugues, S., Koch, S., Gualandi, L., Li, X., Claesson-Welsh, L., Vascular endothelial growth factors and receptors: antiangiogenic therapy in the treatment of cancer (2011) Molecular aspects of medicine., 32, pp. 88-111 De Falco, S., Antiangiogenesis therapy: an update after the first decade (2014) The Korean journal of internal medicine., 29, pp. 1-11 Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Kabbinavar, F., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer (2004) N Engl J Med., 350, pp. 2335-2342 Ferrara, N., Mass, R.D., Campa, C., Kim, R., Targeting VEGF-A to treat cancer and age-related macular degeneration (2007) Annu Rev Med., 58, pp. 491-504 Rofagha, S., Bhisitkul, R.B., Boyer, D.S., Sadda, S.R., Zhang, K., Group, S.-U.S., Seven-year outcomes in ranibizumabtreated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP) (2013) Ophthalmology., 120, pp. 2292-2299 Cao, Y., Positive and negative modulation of angiogenesis by VEGFR1 ligands (2009) Science signaling., 2, p. re1 Dewerchin, M., Carmeliet, P., PlGF: a multitasking cytokine with disease-restricted activity (2012) Cold Spring Harbor perspectives in medicine., p. 2 Fischer, C., Mazzone, M., Jonckx, B., Carmeliet, P., FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? 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R45 Tarallo, V., Vesci, L., Capasso, O., Esposito, M.T., Riccioni, T., Pastore, L., Orlandi, A., De Falco, S., A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGFdependent tumor angiogenesis via heterodimerization (2010) Cancer research., 70, pp. 1804-1813 Nozaki, M., Sakurai, E., Raisler, B.J., Baffi, J.Z., Witta, J., Ogura, Y., Brekken, R.A., Ambati, J., Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A (2006) The Journal of clinical investigation., 116, pp. 422-429}, document_type={Journal Article, }, affiliation={Angiogenesis Lab, Institute of Genetics and Biophysics Adriano Buzzati-Traverso-CNR, Naples, Italy Bio-Ker, MultiMedica Group, Napoli, Italy Department of Clinic Medicine and Surgery, University of Naples Federico II, Italy Institute of Biostructures and Bioimaging-CNR and CIRPeB, University of Naples Federico II, Italy Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, United States Anatomic Pathology Institute, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Italy IRCCS MultiMedica, Milan, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54321, author={Tornatore L, Capece D, D'Andrea D, Begalli F, Verzella D, Bennett J, Acton G, Campbell EA, Kelly J, Tarbit M, Adams N, Bannoo S, Leonardi A, Sandomenico A, Raimondo D, Ruvo M, Chambery A, Oblak M, Al-obaidi MJ, Kaczmarski RS, Gabriel I, Oakervee HE, Kaiser MF, Wechalekar A, Benjamin R, Apperley JF, Auner HW, Franzoso G}, title={Preclinical toxicology and safety pharmacology of the first-in-class GADD45beta/MKK7 inhibitor and clinical candidate, DTP3}, date={2019 Apr 19}, journal={Toxicol Rep (ISSN: 2214-7500linking)}, year={2019}, fullvolume={123}, volume={123}, pages={369--379}, url={}, abstract={Aberrant NF-kappaB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IkappaBalpha kinase (IKK)beta/NF-kappaB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-kappaB-targeting drugs. To overcome this barrier to therapeutic NF-kappaB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)beta/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-kappaB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-kappaB survival signalling in MM and potentially other NF-kappaB-driven cancers.}, keywords={Cancer, Gadd45beta, Multiple Myeloma, Nf-Kappab, Pharmacology, }, references={}, document_type={Journal Article, }, affiliation={CCSI, Department of Medicine, Imperial College London, London, UK., Cancer Research UK Centre for Drug Development, London, UK., C&C Management Consulting Ltd, Exmouth, UK., Alpha Preclinical Consultancy, Halifax, UK., Independent Consultant, Royston, UK., In2Phase Ltd, Welwyn Garden City, UK., Department of Molecular Medicine, University of Naples Federico II, Naples, Italy., IBB-CNR and CIRPeB, "Federico II" University of Naples, Naples, Italy., Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., DiSTABiF, University of Campania "Luigi Vanvitelli", Caserta, Italy., West Middlesex University Hospital, Isleworth, Greater London, UK., Haematology Department, Chelsea and Westminster Hospital, London, UK., London Haematology Limited, London, UK., Barts Cancer Centre, St Bartholomew's Hospital London, London, UK., Division of Molecular Pathology, The Institute of Cancer Research, London, UK., Royal Free London NHS Foundation Trust, London, UK., Department of Haematology, King's College Hospital, London, UK., Centre for Haematology, Imperial College, London, UK., Cancer Cell Protein Metabolism, Department of Medicine, Imperial College London, London, UK., }, ibbaffiliation={1}, } @article{IBB_ID_54259, author={Cimmino I, Margheri F, Prisco F, Perruolo G, D'Esposito V, Laurenzana A, Fibbi G, Paciello O, Doti N, Ruvo M, Miele C, Beguinot F, Formisano P, Oriente F}, title={Prep1 regulates angiogenesis through a PGC-1alpha-mediated mechanism}, date={2019 Oct 15}, journal={Faseb J (ISSN: 0892-6638linking)}, year={2019}, fullvolume={197}, volume={197}, pages={13893--13904}, url={}, abstract={Angiogenesis depends on a delicate balance between the different transcription factors, and their control should be considered necessary for preventing or treating diseases. Pre-B-cell leukemia transcription factor regulating protein 1 (Prep1) is a homeodomain transcription factor that plays a primary role in organogenesis and metabolism. Observations performed in a Prep1 hypomorphic mouse model, expressing 3-5% of the protein, show an increase of embryonic lethality due, in part, to defects in angiogenesis. In this study, we provide evidence that overexpression of Prep1 in mouse aortic endothelial cells (MAECs) stimulates migration, proliferation, and tube formation. These effects are paralleled by an increase of several proangiogenic factors and by a decrease of the antiangiogenic gene neurogenic locus notch homolog protein 1 (Notch1). Prep1-mediated angiogenesis involves the activation of the p160 Myb-binding protein (p160)/peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) pathway. Indeed, Prep1 overexpression increases its binding with p160 and induces a 4-fold increase of p160 and 70% reduction of PGC-1alpha compared with control cells. Incubation of MAECs with a synthetic Prep1(54-72) peptide, mimicking the Prep1 region involved in the interaction with p160, reverts the proangiogenic effects mediated by Prep1. In addition, Prep1 levels increase by 3.2-fold during the fibroblast growth factor beta (bFGF)-mediated endothelial colony-forming cells' activation, whereas Prep1(54-72) peptide reduces the capability of these cells to generate tubular-like structures in response to bFGF, suggesting a possible role of Prep1 both in angiogenesis from preexisting vessels and in postnatal vasculogenesis. Finally, Prep1 hypomorphic heterozygous mice, expressing low levels of Prep1, show attenuated placental angiogenesis and vessel formation within Matrigel plugs. All of these observations indicate that Prep1, complexing with p160, decreases PGC-1alpha and stimulates angiogenesis.-Cimmino, I., Margheri, F., Prisco, F., Perruolo, G., D'Esposito, V., Laurenzana, A., Fibbi, G., Paciello, O., Doti, N., Ruvo, M., Miele, C., Beguinot, F., Formisano, P., Oriente, F. Prep1 regulates angiogenesis through a PGC-1alpha-mediated mechanism.}, keywords={Pgc-1alpha Inhibition, Tale Homeodomain Proteins, P160, Animals , Cell Movement Physiology , Cell Proliferation Physiology , Cultured , Endothelial Cells Metabolism , Gene Expression Regulation Physiology , Homeodomain Proteins Metabolism , Mice , Neovascularization, Pathologic Metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha Metabolism , Pgc-1α Inhibition, }, references={}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, }, affiliation={Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), University of Naples Federico II, Naples, Italy. Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy. Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy. Institute of Biostructure and Bioimaging, National Research Council-Interuniversity Research Centre on Bioactive Peptides, Naples, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_12492, author={Palladino P, Ronga L, Tizzano B, Rossi F, Ragone R, Tancredi T, Saviano G, Facchiano A, Costantini S, Ruvo M, Benedetti E}, title={Prion protein misfolding: Conformational stability of the alpha 2-helix}, date={2006}, journal={Understanding Biology Using Peptides}, year={2006}, fullvolume={262}, volume={262}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_53860, author={Rega C, Russo R, Foca A, Sandomenico A, Iaccarino E, Raimondo D, Milanetti E, Tornatore L, Franzoso G, Pedone PV, Ruvo M, Chambery A}, title={Probing the interaction interface of the GADD45beta/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry}, date={2018 Jul 15}, journal={Int J Biol Macromol (ISSN: 1879-0003electronic, 0141-8130linking)}, year={2018}, fullvolume={255}, volume={255}, pages={114--123}, url={}, abstract={GADD45beta is selectively and constitutively expressed in Multiple Myeloma cells, and this expression correlates with an unfavourable clinical outcome. GADD45beta physically interacts with the JNK kinase, MKK7, inhibiting its activity to enable the survival of cancer cells. DTP3 is a small peptide inhibitor of the GADD45beta/MKK7 complex and is able to restore MKK7/JNK activation, thereby promoting selective cell death of GADD45beta-overexpressing cancer cells. Enzymatic MS foot-printing and diazirine-based chemical cross-linking MS (CX-MS) strategies were applied to study the interactions between GADD45beta and MKK7 kinase domain (MKK7_KD) and between DTP3 and MKK7_KD. Our data show that the binding between GADD45beta and MKK7 largely occurs between GADD45beta loop 2 (region 103-117) and the kinase enzymatic pocket. We also show that DTP3 interferes with this GADD45beta/MKK7 interaction by contacting the MKK7 peptides, 113-136 and 259-274. Accordingly, an MKK7_KD Delta(101-136) variant lacking Trp135 did not produce a fluorescence quenching effect upon the binding of DTP3. The assessment of the interaction between GADD45beta and MKK7 and the elucidation of the recognition surfaces between DTP3 and MKK7 significantly advance the understanding of the mechanism underlying the inhibition of the GADD45beta/MKK7 interaction by DTP3 and pave the way to the design of small-molecule DTP3 analogues.}, keywords={Chemical Cross-Linking, Gadd45beta, Mkk7, Mass Spectrometry, Protein-Protein Interaction, }, references={}, document_type={Journal Article, }, affiliation={Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy., CNR-IBB, 80134 Napoli, Italy., Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy., Department of Physics, Sapienza University of Rome, 00161 Rome, Italy., Department of Medicine, Centre for Cell Signalling and Inflammation, Imperial College London, London W12 0NN, UK., CNR-IBB, 80134 Napoli, Italy. Electronic address: menotti.ruvo@unina.it., Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. Electronic address: angela.chambery@unicampania.it., }, ibbaffiliation={1}, } @article{IBB_ID_51866, author={Galdiero S, Capasso D, Vitiello M, D'Isanto M, Di Niola E, Monti S, Ruvo M, Pedone C, Galdiero M}, title={Protein P2 from Haemophilus influenzae: The role of its surface exposed loops on the mitogen-activated protein kinase cascade}, date={2004}, journal={Peptide Revolution}, year={2004}, fullvolume={290}, volume={290}, pages={N/D--N/D}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, Abstract, Conference, }, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_9068, author={Sandomenico A, Monti SM, Sabatella M, De Capua A, Tornatore L, Doti N, Viparelli F, Dathan NA, Pedone C, Ruvo M, Marasco D}, title={Protein-protein interactions: a simple strategy to identify binding sites and peptide antagonists}, date={2009 May}, journal={Chem Biol Drug Des (ISSN: 1747-0285, 1747-0277)}, year={2009}, fullvolume={435}, volume={435}, pages={483--493}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-64249105372&partnerID=40&md5=85412fb9e85fd7bfb3c6c99e13198431}, abstract={Secondary structure motifs and small protein domains can act as building blocks that are isolated and investigated to gain insights into protein global structure but can also modulate interactions with external partners. Most progress has been made in this field using synthetic peptides. Fragmentation of folded proteins by proteolytic enzymes that act preferentially on exposed and less structured sites can help to isolate shorter polypeptides with preserved secondary and tertiary structures that mimic the original protein architecture. Such molecules can be used as probes for structural studies and as tools for in vitro assays to select active fragments useful as agonists or antagonists of the original protein or as scaffolds for the design of more potent and selective ligands. This simple but effective proteolytic methodology has been successfully applied to determine antagonists of protein-protein interactions, allowing the identification of inhibitors with high efficacy and specificity. Here, we present several studies including the complex between phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes and phospholipase 1, believed to play a relevant role in the insulin resistance mechanism in phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-overexpressing tissues, the self-association of BCL10 caspase recruitment domain that mediates a protein oligomerization process responsible for NF-kappaB activation and the self-association of growth arrest and DNA damage-inducible factor 45 beta, a major player of the endogenous NF-kappaB-mediated resistance to apoptosis.}, keywords={Competition Assays, Mass Spectrometry, Proteolysis, Synthetic Peptides, Growth Arrest And Dna Damage Inducible Protein 45, Immunoglobulin Enhancer Binding Protein, Peptide Antagonist, Peptide Antibody, Phospholipase, Phosphoprotein, Protein Bcl 10, Unclassified Drug, Article, Binding Site, Circular Dichroism, Diabetes Mellitus, Gene Overexpression, In Vitro Study, Liquid Chromatography, Nonhuman, Peptide Synthesis, Priority Journal, Protein Degradation, Protein Domain, Protein Folding, Protein Protein Interaction, Protein Secondary Structure, Protein Structure, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antigens, Differentiation, Intracellular Signaling Peptides And Proteins, Molecular Sequence Data, Multiprotein Complexes, Nf-Kappa B, Protein Binding, Protein Interaction Mapping, Tertiary, }, references={Jones, S., Thornton, J.M., Principles of protein-protein interactions (1996) Proc Natl Acad Sci U S A, 93, pp. 13-2 Zhao, L., Chmielewski, J., Inhibiting Protein-Protein Interactions Using Designed Molecules (2005) Curr Opin Struct Biol, 15, pp. 31-34 Fontana, A., De Laureto, P.P., Spolaore, B., Frare, E., Picotti, P., Zambonin, M., Probing protein structure by limited proteolysis (2004) Acta Biochimica Polonica, 51, pp. 299-321 Spagnuolo, M.S., Cigliano, L., D'Andrea, L.D., Pedone, C., Abrescia, P., Assignment of the binding site for haptoglobin on apolipoprotein A-I (2005) J Biol Chem, 280, pp. 1193-1198 Anders, D.G., Consigli, R.A., Chemical cleavage of polyomavirus major structural protein VP1: Identification of cleavage products and evidence that the receptor moiety resides in the carboxy-terminal region (1983) J Virol, 48, pp. 197-205 Papa, S., Monti, S.M., Vitale, R.M., Bubici, C., Jayawardena, S., Alvarez, K., De Smaele, E., Franzoso, G., Insights into the structural basis of the GADD45beta-mediated inactivation of the JNK kinase, MKK7/JNKK2 (2007) J. Biol Chem, 282, pp. 19029-19041 Hamady, M., Cheung, T.H., Tufo, H., Knight, R., Does protein structure influence trypsin miscleavage? Using structural properties to predict the behavior of related proteins (2005) IEEE Eng Med Biol Mag, 24, pp. 58-66 Vigliotta, G., Miele, C., Santopietro, S., Portella, G., Perfetti, A., Maitan, M.A., Cassese, A., Beguinot, F., Overexpression of the ped/pea-15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action (2004) Mol Cell Biol, 24, pp. 5005-15 Condorelli, G., Vigliotta, G., Iavarone, C., Caruso, M., Tocchetti, C.G., Andreozzi, F., Cafieri, A., Beguinot, F., PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus (1998) Embo J, 17, pp. 3858-66 Viparelli, F., Cassese, A., Doti, N., Paturzo, F., Marasco, D., Dathan, N.A., Monti, S.M., Ruvo, M., Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells (2008) J Biol Chem, 283, pp. 21769-21778 De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D.U., Jin, R., Jones, J., Cong, R., Franzoso, G., Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signaling (2001) Nature, 414, pp. 308-13 Schrag, J.D., Jiralerspong, S., Banville, M., Jaramillo, M.L., O'Connor-Mccourt, M.D., The crystal structure and dimerization interface of GADD45gamma (2008) Proc Natl Acad Sci U S A, 105, pp. 6566-71 Kovalsky, O., Lung, F.D., Roller, P.P., Fornace Jr., A.J., (2001) Oligomerization of Human Gadd45a Protein J Biol Chem, 276, pp. 39330-9 Tornatore, L., Marasco, D., Dathan, N., Vitale, R.M., Benedetti, E., Papa, S., Franzoso, G., Monti, S.M., Gadd45 beta forms a homodimeric complex that binds tightly to MKK7 (2008) J Mol Biol, 378, pp. 97-111 Hofmann, K., Bucher, P., Tschopp, J., The CARD domain: A new apoptotic signalling motif (1997) Trends Biochem Sci, 22, pp. 155-6 Guiet, C., Vito, P., Caspase recruitment domain (CARD)-dependent cytoplasmic filaments mediate bcl10-induced NF-kappaB activation (2000) J Cell Biol, 148, pp. 1131-40 Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int. J. Pept. Protein Res, 35, pp. 161-214 Viparelli, F., Doti, N., Sandomenico, A., Marasco, D., Dathan, N.A., Miele, C., Beguinot, F., Ruvo, M., Expression and purification of the D4 region of PLD1 and characterization of its interaction with PED-PEA15 (2008) Protein Expr Purif, 59, pp. 302-8 Zhang, Y., Redina, O., Altshuller, Y.M., Yamazaki, M., Ramos, J., Chneiweiss, H., Kanaho, Y., Frohman, M.A., Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them (2000) J Biol Chem, 275, pp. 35224-32 West, G.M., Tang, L., Fitzgerald, M.C., Thermodynamic analysis of protein stability and ligand binding using a chemical modification- and mass spectrometry-based strategy (2008) Anal Chem, 80, pp. 4175-85 Hill, J.M., Vaidyanathan, H., Ramos, J.W., Ginsberg, M.H., Werner, M.H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) Embo J, 21, pp. 6494-504 Skrabanek, L., Saini, H.K., Bader, G.D., Enright, A.J., Computational prediction of protein-protein interactions (2008) Mol. Biotechnol, 38, pp. 1-17 Gomez, S.M., Choi, K., Wu, Y., Prediction of protein-protein interaction networks (2008) Curr. Protoc. Bioinformatics, pp. 821-8214 Polverino De Laureto, P., Frare, E., Gottardo, R., Van Dael, H., Fontana, A., Partly folded states of members of the lysozyme/lactalbumin superfamily: A comparative study by circular dichroism spectroscopy and limited proteolysis (2002) Protein Science, 11, pp. 2932-2946 Spagnuolo, M. S., Cigliano, L., D'Andrea, L. D., Pedone, C., Abrescia, P., Assignment of the binding site for haptoglobin on apolipoprotein A-I (2005) J Biol Chem, 280, pp. 1193-1198 Anders, D. G., Consigli, R. A., Chemical cleavage of polyomavirus major structural protein VP1: Identification of cleavage products and evidence that the receptor moiety resides in the carboxy-terminal region (1983) J Virol, 48, pp. 197-205 Schrag, J. D., Jiralerspong, S., Banville, M., Jaramillo, M. L., O'Connor-Mccourt, M. D., The crystal structure and dimerization interface of GADD45gamma (2008) Proc Natl Acad Sci U S A, 105, pp. 6566-71 Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int. J. Pept. Protein Res, 35, pp. 161-214 West, G. M., Tang, L., Fitzgerald, M. C., Thermodynamic analysis of protein stability and ligand binding using a chemical modification- and mass spectrometry-based strategy (2008) Anal Chem, 80, pp. 4175-85 Hill, J. M., Vaidyanathan, H., Ramos, J. W., Ginsberg, M. H., Werner, M. H., Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain (2002) Embo J, 21, pp. 6494-504 Gomez, S. M., Choi, K., Wu, Y., Prediction of protein-protein interaction networks (2008) Curr. Protoc. Bioinformatics, pp. 821-8214}, document_type={Journal Article, Research Support, Non-U. S. Gov'T, Validation Studies, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134, Napoli, Italy. Centro di Ricerca Interdipartimentale sui Biomateriali, Università di Napoli Federico II, P.le Tecchio, 80-80125 Napoli, Italy Dipartimento Delle Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone 16, 80134 Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_9069, author={Chambery A, Vissers JPC, Langridge JI, Lonardo E, Minchiotti G, Ruvo M, Parente A}, title={Qualitative and quantitative proteomic profiling of cripto-1- embryonic stem cells by means of accurate mass LC-MS analysis}, date={2009}, journal={J Proteome Res (ISSN: 1535-3893)}, year={2009}, fullvolume={820}, volume={820}, pages={1047--1058}, url={}, abstract={Cripto is one of the key regulators of embryonic stem cells (ESCs) differentiation into cardiomyocites vs neuronal fate. Cripto-/- murine ESCs have been utilized to investigate the molecular mechanisms underlying early events of mammalian lineage differentiation. 2D/LC-MS/MS and a label-free LC-MS approaches were used to qualitatively and quantitatively profile the cripto-/- ESC proteome, providing an integral view of the alterations induced in stem cell functions by deleting the cripto gene. © 2009 American Chemical Society.}, keywords={Cripto, Data Independent Scanning, Hsp25, Lc-Ms, Mass Spectrometry, Proteomic Profiling, Epidermal Growth Factor, Protein Cripto, Unclassified Drug, Animal Cell, Article, Cell Differentiation, Controlled Study, Dna Fingerprinting, Embryonic Stem Cell, Enzyme Regulation, Liquid Chromatography, Mouse, Nonhuman, Nucleotide Sequence, Priority Journal, Protein Binding, Protein Expression, Protein Folding, Cultured, Membrane Glycoproteins, Knockout, Molecular Sequence Data, Neoplasm Proteins, Neurons, Protein Array Analysis, Reproducibility Of Results, Mammalia, Murinae, }, references={Skalnikova, H., Halada, P., Vodicka, P., Motlik, J., Rehulka, P., Horning, O., Chmelik, J., Kovarova, H., A proteomic approach to studying the differentiation of neural stem cells (2007) Proteomics, 7 (11), pp. 1825-183 Rolfs, A. 2-DE proteome analysis of a proliferating and differentiating human neuronal stem cell line (ReNceU VM). Proteomics 2006, 6 (6), 1833-17Van Hoof, D., Passier, R., Ward-Van Oostwaard, D., Pinkse, M.W., Heck, A.J., Mummery, C.L., Krijgsveld, J., A quest for human and mouse embryonic stem cell-specific proteins (2006) Mol Cell Proteomics, 5 (7), pp. 1261-1273 Baharvand, H., Hajheidari, M., Ashtiani, S.K., Salekdeh, G.H., Proteomic signature of human embryonic stem cells (2006) Proteomics, 6 (12), pp. 3544-3549 Vodicka, P., Skalnikova, H., Kovarova, H., The characterization of stem cell proteomes (2006) Curr. Opin. Mol. Ther, 8 (3), pp. 232-239 Hoffrogge, R., Beyer, S., Volker, U., Uhrmacher, A.M., Rolfs, A., 2-DE proteomic profiling of neuronal stem cells (2006) Neurodegener. Dis, 3 (1-2), pp. 112-121 Veenstra, T. D. Proteomic profiling of differentiating osteoblasts. Expert Rev. Proteomics 2006, 3 (5), 483- 96Hayman, M.W., Christie, V.B., Keating, T.S., Przyborski, S.A., Following the differentiation of human pluripotent stem cells by proteomic identification of biomarkers (2006) Stem Cells Dev, 15 (2), pp. 221-231 Prudhomme, W., Daley, G.Q., Zandstra, P., Lauffenburger, D.A., Multivariate proteomic analysis of murine embryonic stem cell self-renewal versus differentiation signaling (2004) Proc. Natl Acad. Sci. U.SA, 101 (9), pp. 2900-2905 Nagano, K., Taoka, M., Yamauchi, Y., Itagaki, C., Shinkawa, T., Nunomura, K., Okamura, N., Isobe, T., Large-scale identification of proteins expressed in mouse embryonic stem cells (2005) Proteomics, 5 (5), pp. 1346-1361 Wang, D., Gao, L., Proteomic analysis of neural differentiation of mouse embryonic stem cells (2005) Proteomics, 5 (17), pp. 4414-4426 Guo, X., Ting, W., Wan, J., Hu, Z., Qian, X., Zhang, H., He, F., Proteomic characterization of early-stage differentiation of mouse embryonic stem cells into neural cells induced by all-trans retinoic acid in vitro (2001) Electrophoresis, 22 (14), pp. 3067-3075 Elliott, S.T., Crider, D.G., Garnham, C.P., Boheler, K.R., Van Eyk, J.E., Two-dimensional gel electrophoresis database of murine Rl embryonic stem cells (2004) Proteomics, 4 (12), pp. 3813-3832 Hayman, M.W., Przyborski, S.A., Proteomic identification of biomarkers expressed by human pluripotent stem cells (2004) Biochem. Biophys. Res. 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Z., Golick, D., Gorenstein, M., Silva, J. C., Vissers, J. P., Geromanos, S., A novel ion accounting algorithm for protein database searches (2006) 5th HUPO Annual World Congress, , Poster W079 presented at the, Long Beach, CA Vissers, J. P., Langridge, J. I., Aerts, J. M., Analysis and quantification of diagnostic serum markers and protein signatures for Gaucher disease (2007) Mol. Cell Proteomics, 6 (5), pp. 755-766 Palmieri, S. L., Peter, W., Hess, H., Scholer, H. R., Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation (1994) Dev. Biol, 166 (1), pp. 259-267 Parish, C. L., Parisi, S., Persico, M. G., Arenas, E., Minchiotti, G., Cripto as a target for improving embryonic stem cell-based therapy in Parkinson's disease (2005) Stem Cells, 23 (4), pp. 471-476 Christians, E. S., Zhou, Q., Renard, J., Benjamin, I. J., Heat shock proteins in mammalian development (2003) Semin. 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J., Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human embryonic stem cells and downregulated upon differentiation (2005) Stem Cells, 23 (10), pp. 1502-1513 Seo, H. R., Chung, D. Y., Lee, Y. J., Lee, D. H., Kim, J. I., Bae, S., Chung, H. Y., Lee, Y. S., Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: Dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation (2006) J. Biol. Chem, 281 (25), pp. 17220-17227 Caplan, A. J., Mandal, A. K., Theodoraki, M. A., Molecular chaperones and protein kinase quality control (2007) Trends Cell Biol, 17 (2), pp. 87-92 Barnier, J. V., Bensaude, O., Morange, M., Babinet, C., Mouse 89 kD heat shock protein. Two polypeptides with distinct developmental regulation (1987) Exp. Cell Res, 170 (1), pp. 186-194 Sun, H. B., Neff, A. W., Mescher, A. L., Malacinski, G. M., Expression of the axolotl homologue of mouse chaperonin t-complex protein-1 during early development (1995) Biochim. Biophys. Acta, 1260 (2), pp. 157-166 Wang, A. H., Yang, X. J., Histone deacetylase 4 possesses intrinsic nuclear import and export signals (2001) Mol. Cell. Biol, 21 (17), pp. 5992-6005 McCool, K. W., Xu, X., Singer, D. B., Murdoch, F. E., Fritsch, M. K., The role of histone acetylation in regulating early gene expression patterns during early embryonic stem cell differentiation (2007) J. Biol. Chem, 282 (9), pp. 6696-6706 Skoulakis, E. M., Davis, R. L., 14-3-3 proteins in neuronal development and function (1998) Mol. Neurobiol, 16 (3), pp. 269-284 Tien, A. C., Hsei, H. Y., Chien, C. T., Dynamic expression and cellular localization of the drosophila 14-3-3epsilon during embryonic development (1999) Mech. Dev, 81 (1-2), pp. 209-212 van Erp, H. E., Rijksen, G., van der Saag, P. T., Staal, G. E., Phosphofructokinase and pyruvate kinase in mouse embryonal carcinoma P19 cells in relation to growth and differentiation (1990) Differentiation, 45 (3), pp. 199-205 Park, Y. J., Luger, K., Structure and function of nucleosome assembly proteins (2006) Biochem Cell Biol, 84 (4), pp. 549-558}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze della Vita, Seconda Università di Napoli, 1-81100 Caserta, Italy Waters Corporation, MS Technologies Center, M22 5PP Manchester, United Kingdom Istituto di Genetica e Biofisica A Buzzati-Traverso, CNR, 1-80131 Napoli, Italy Istituto di Biostrutture e Bioimmagini, CNR, 1-80134, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_9070, author={Chambery A, Severino V, Di Maro A, D'Aniello A, Ruvo M, Parente A}, title={Quantification of thyrotropin-releasing hormone by liquid chromatography-electrospray mass spectrometry}, date={2010 Apr}, journal={Amino Acids (ISSN: 0939-4451, 1438-2199, 1438-2199electronic)}, year={2010}, fullvolume={405}, volume={405}, pages={1031--1041}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77951667550&partnerID=40&md5=4999ecbfe31522dc96c464bb485dfc6a}, abstract={Thyrotropin-releasing hormone (TRH) is involved in a wide range of biological responses. It has a central role in the endocrine system and regulates several neurobiological activities. In the present study, a rapid, sensitive and selective liquid chromatography-mass spectrometry method for the identification and quantification of TRH has been developed. The methodology takes advantage of the specificity of the selected-ion monitoring acquisition mode with a limit of detection of 1 fmol. Furthermore, the MS/MS fragmentation pattern of TRH has been investigated to develop a selected reaction monitoring (SRM) method that allows the detection of a specific b2 product ion at m/z 249.1, corresponding to the N-terminus dipeptide pyroglutamic acid-histidine. The method has been tested on rat hypothalami to evaluate its suitability for the detection within very complex biological samples. © 2009 Springer-Verlag.}, keywords={Liquid Chromatography, Mass Spectrometry, Selected Reaction Monitoring, Selected-Ion Monitoring, Thyrotropin-Releasing Hormone, Dipeptide, Histidine, Protirelin, Pyroglutamic Acid, Amino Terminal Sequence, Analytic Method, Animal Tissue, Article, Chemical Reaction, Controlled Study, Electrospray, Electrospray Mass Spectrometry, Hypothalamus, Nonhuman, Priority Journal, Protein Analysis, Protein Synthesis, Qualitative Analysis, Quantitative Analysis, Reaction Analysis, Sensitivity And Specificity, Amino Acids, Calibration, High Pressure Liquid, Reverse-Phase, Limit Of Detection, Microchemistry, Molecular Structure, Pyrrolidonecarboxylic Acid, Reproducibility Of Results, Electrospray Ionization, Tandem Mass Spectrometry, Rattus, }, references={Badiu, C., Ham, J., Carnu, R., Coculescu, M., TRH synthesis in "mute" thyrotropinomas: Cause-effect or coincidence? 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M., Thyrotropin-releasing hormone (TRH) reverses hyperglycemia in rat (2008) Biochem Biophys Res Commun, 374, pp. 69-73. , 10. 1016/j. bbrc. 2008. 06. 111 10. 1016/j. bbrc. 2008. 06. 111 1: CAS: 528: DC%2BD1cXptVKjs7w%3D 18602893 Nillni, E. A., Vaslet, C., Harris, M., Hollenberg, A., Bjorbak, C., Flier, J. S., Leptin regulates prothyrotropin-releasing hormone biosynthesis: Evidence for direct and indirect pathways (2000) J Biol Chem, 275, pp. 36124-36133. , 10. 1074/jbc. M003549200 10. 1074/jbc. M003549200 1: CAS: 528: DC%2BD3cXosVSku78%3D 10967095 Prange Jr, A. J., Lara, P. P., Wilson, I. C., Alltop, L. B., Breese, G. R., Effects of thyrotropin-releasing hormone in depression (1972) Lancet, 2, pp. 999-1002. , 10. 1016/S0140-6736 (72) 92407-5 10. 1016/S0140-6736 (72) 92407-5 4116985 Strand, F. L., Neuropeptides: General characteristics and neuropharmaceutical potential in treating CNS disorders (2003) Prog Drug Res, 61, pp. 1-37. , 1: CAS: 528: DC%2BD3sXpvFert7k%3D 14674607 Visser, T. J., Docter, R., Hennemann, G., Radioimmunoassay of thyrotrophin releasing hormone (TRH) (1974) Acta Endocrinol (Copenhagen), 77, pp. 417-421. , 1: CAS: 528: DyaE2MXltlKqtg%3D%3D Visser, T. J., Klootwijk, W., Docter, R., Hennemann, G., A new radioimmunoassay of thyrotropin-releasing hormone (1977) FEBS Letters, 83 (1), pp. 37-40. , DOI 10. 1016/0014-5793 (77) 80636-4 Warner, A. M., Weber, S. G., Electrochemical detection of peptides (1989) Anal Chem, 61, pp. 2664-2668. , 10. 1021/ac00198a015 10. 1021/ac00198a015 1: CAS: 528: DyaL1MXmsVOhtbs%3D 2619052 Zhao, Y., Hou, W. G., Zhu, H. P., Zhao, J., Wang, R. A., Xu, R. J., Zhang, Y. Q., Expression of thyrotropin-releasing hormone receptors in rat testis and their role in isolated Leydig cells (2008) Cell Tissue Res, 334, pp. 283-294. , 10. 1007/s00441-008-0680-y 10. 1007/s00441-008-0680-y 1: CAS: 528: DC%2BD1cXhtlCjsrjF 18795335}, document_type={Journal Article, }, affiliation={Dipartimento di Scienze della Vita, Seconda Università di Napoli, Via Vivaldi 43, Caserta 81100, Italy Laboratorio di Fisiologia Animale Ed Evoluzione, Stazione Zoologica 'A. Dohrn', Villa Comunale, Naples 80121, Italy Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, Naples 80134, Italy}, ibbaffiliation={1}, } @article{IBB_ID_54649, author={Doti N, Mardirossian M, Sandomenico A, Ruvo M, Caporale A}, title={Recent Applications of Retro-Inverso Peptides}, date={2021 Aug 12}, journal={Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596)}, year={2021}, fullvolume={15}, volume={15}, pages={N/D--N/D}, url={}, abstract={Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.}, keywords={Amino Acid Sequence, Animals, Humans, Peptides Chemical Synthesis Genetics Pharmacology, Protein Conformation, Iapp, Anticancer Peptides, Antimicrobial Peptides, Drug Delivery, Peptide Antigens, Retro-Inverso Peptides, Aβ}, references={}, document_type={Journal Article, Review}, affiliation={Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80134 Napoli, Italy. Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy. Institute of Crystallography (IC), National Research Council (CNR), 34149 Trieste, Italy.}, ibbaffiliation={1}, } @article{IBB_ID_53624, author={Doti N, Ruvo M}, title={Relevance and therapeutic potential of CypA targeting to block apoptosis inducing factor-mediated neuronal cell death}, date={2017 Sep}, journal={Neural Regen Res (ISSN: 1673-5374)}, year={2017}, fullvolume={347}, volume={347}, pages={1428--1429}, url={}, abstract={}, keywords={, }, references={}, document_type={Journal Article, }, affiliation={Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone, 16, 80134 Napoli, Italy., }, ibbaffiliation={1}, } @article{IBB_ID_54825, author={Conte M, Palumbo R, Monti A, Fontana E, Nebbioso A, Ruvo M, Altucci L, Doti N}, title={Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine}, date={2022}, journal={Int J Mol Sci}, year={2022}, fullvolume={14}, volume={14}, pages={265--265}, url={}, abstract={}, keywords={}, references={}, document_type={Abstract, Conference}, affiliation={}, ibbaffiliation={1}, } @article{IBB_ID_8940, author={Doti N, Cassese A, Marasco D, Paturzo F, Sabatella M, Viparelli F, Dathan N, Monti SM, Miele C, Formisano P, Beguinot F, Ruvo M}, title={Residues 762-801 of PLD1 mediate the interaction with PED/PEA15}, date={2010 Oct}, journal={Mol Biosyst (ISSN: 1742-206x)}, year={2010}, fullvolume={454}, volume={454}, pages={2039--2048}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77956522887&partnerID=40&md5=eca30cf85825325adc033ad504d7c666}, abstract={The interaction of Phospholipase D1 (PLD1) by its C-terminal domain D4 with PED/PEA15 has been indicated as a target for type 2 diabetes. PED/PEA15 is overexpressed in several tissues of individuals affected by type 2 diabetes and its overexpression in intact cells and in transgenic animal models impairs insulin regulation of glucose transport by a mechanism mediated by the interaction with D4 and the consequent increase of protein kinase C-α activity. Expression of D4 or administration of a peptide mimicking the PED/PEA15 region involved in this interaction to cells stably overexpressing PED/PEA15 reduces its interaction with PLD1, thereby lowering PKC-α activation and restoring normal glucose transport mediated by PKC-ζ. By using D4 deletion mutants, we have restricted the PLD1 region involved in PED/PEA15 interaction to an N-terminal fragment named D4α (residues 712-818). This region binds PED/PEA15 with the same efficacy as D4 (K D ∼ 0.7 μM) and, when transfected in different PED/PEA15-overexpressing cells, it is able to reduce PKC-α activity and to restore the sensitivity of PKC-ζ to insulin stimulation, independently of the PI3K/Akt signalling. We also show that the effective disruption of the PED/PEA15-PLD1 interaction can restore the normal ERK1/2 signalling. Finally, using a set of overlapping peptides that cover the D4α region, we have further restricted the shortest PED/PEA15-binding site to a segment encompassing residues 762-801, suggesting that a quite limited binding interface mostly contributes to the interaction and can thus be a selective target for the design of effective antagonists. © 2010 The Royal Society of Chemistry.}, keywords={Pea15 Protein, Human, Phospholipase D, Phosphoprotein, Primer Dna, Signal Peptide, Article, Chemistry, Metabolism, Nucleotide Sequence, Protein Binding, Signal Transduction, Site Directed Mutagenesis, Base Sequence, Dna Primers, Intracellular Signaling Peptides And Proteins, Site-Directed, Animalia, }, references={Huang, H., Frohman, M.A., (2009) Biochim. Biophys. Acta, Mol. Cell Biol. Lipids, 1791, pp. 839-4 Cummings, R., Parinandi, N., Wang, L., Usatyuk, P., Natarajan, V., (2002) Mol. Cell. Biochem., 234-235, pp. 99-109 Sung, T.C., Roper, R.L., Zhang, Y., Rudge, S.A., Temel, R., Hammond, S.M., Morris, A.J., Frohman, M.A., (1997) EMBO J., 16, pp. 4519-30 Hammond, S.M., Jenco, J.M., Nakashima, S., Cadwallader, K., Gu, Q., Cook, S., Nozawa, Y., Morris, A.J., (1997) J. Biol. Chem., 272, pp. 3860-8 Powner, D.J., Wakelam, M.J., (2002) FEBS Lett., 531, pp. 62-4 Exton, J.H., (2002) FEBS Lett., 531, pp. 58-61 Condorelli, G., Vigliotta, G., Iavarone, C., Caruso, M., Tocchetti, C.G., Andreozzi, F., Cafieri, A., Beguinot, F., (1998) EMBO J., 17, pp. 3858-66 Valentino, R., Lupoli, G.A., Raciti, G.A., Oriente, F., Farinaro, E., Della Valle, E., Salomone, M., Beguinot, F., (2006) Diabetologia, 49, pp. 3058-66 Ungaro, P., Teperino, R., Mirra, P., Cassese, A., Fiory, F., Perruolo, G., Miele, C., Beguinot, F., (2008) J. Biol. Chem., 283, pp. 30970-9 Vigliotta, G., Miele, C., Santopietro, S., Portella, G., Perfetti, A., Maitan, M.A., Cassese, A., Beguinot, F., (2004) Mol. Cell. Biol., 24, pp. 5005-15 Zhang, Y., Redina, O., Altshuller, Y.M., Yamazaki, M., Ramos, J., Chneiweiss, H., Kanaho, Y., Frohman, M.A., (2000) J. Biol. Chem., 275, pp. 35224-32 Viparelli, F., Doti, N., Sandomenico, A., Marasco, D., Dathan, N.A., Miele, C., Beguinot, F., Ruvo, M., (2008) Protein Expression Purif., 59, pp. 302-8 Viparelli, F., Cassese, A., Doti, N., Paturzo, F., Marasco, D., Dathan, N.A., Monti, S.M., Ruvo, M., (2008) J. Biol. Chem., 283, pp. 21769-78 Formstecher, E., Ramos, J.W., Fauquet, M., Calderwood, D.A., Hsieh, J.C., Canton, B., Nguyen, X.T., Chneiweiss, H., (2001) Dev. Cell, 1, pp. 239-50 Ramos, J.W., Hughes, P.E., Renshaw, M.W., Schwartz, M.A., Formstecher, E., Chneiweiss, H., Ginsberg, M.H., (2000) Mol. Biol. Cell, 11, pp. 2863-72 Condorelli, G., Trencia, A., Vigliotta, G., Perfetti, A., Goglia, U., Cassese, A., Musti, A.M., Beguinot, F., (2002) J. Biol. Chem., 277, pp. 11013-8 Fields, G.B., Noble, R.L., (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Xie, Z., Ho, W.T., Exton, J.H., (2000) Eur. J. Biochem., 267, pp. 7138-46 Hill, J.M., Vaidyanathan, H., Ramos, J.W., Ginsberg, M.H., Werner, M.H., (2002) EMBO J., 21, pp. 6494-504 Zhao, Y., Stuckey, J.A., Lohse, D.L., Dixon, J.E., (1997) Protein Sci., 6, pp. 2655-8 Sung, T. C., Roper, R. L., Zhang, Y., Rudge, S. A., Temel, R., Hammond, S. M., Morris, A. J., Frohman, M. A., (1997) EMBO J., 16, pp. 4519-30 Hammond, S. M., Jenco, J. M., Nakashima, S., Cadwallader, K., Gu, Q., Cook, S., Nozawa, Y., Morris, A. J., (1997) J. Biol. Chem., 272, pp. 3860-8 Powner, D. J., Wakelam, M. J., (2002) FEBS Lett., 531, pp. 62-4 Exton, J. H., (2002) FEBS Lett., 531, pp. 58-61 Ramos, J. W., Hughes, P. E., Renshaw, M. W., Schwartz, M. A., Formstecher, E., Chneiweiss, H., Ginsberg, M. H., (2000) Mol. Biol. Cell, 11, pp. 2863-72 Fields, G. B., Noble, R. L., (1990) Int. J. Pept. Protein Res., 35, pp. 161-214 Xie, Z., Ho, W. T., Exton, J. H., (2000) Eur. J. Biochem., 267, pp. 7138-46 Hill, J. M., Vaidyanathan, H., Ramos, J. W., Ginsberg, M. H., Werner, M. H., (2002) EMBO J., 21, pp. 6494-504}, document_type={Journal Article, }, affiliation={Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone 16, 80134, Napoli, Italy Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Napoli, Italy Dipartimento Delle Scienze Biologiche, Università di Napoli Federico II, via Mezzocannone 16, 80134, Napoli, Italy Istituto di Endocrinologia e Oncologia Sperimentale Gaetano Salvatore, Consiglio Nazionale Delle Ricerche, Napoli, Italy}, ibbaffiliation={1}, } @article{IBB_ID_53949, author={Carafa V, Nebbioso A, Cuomo F, Rotili D, Cobellis G, Bontempo P, Baldi A, Spugnini EP, Citro G, Chambery A, Russo R, Ruvo M, Ciana P, Maravigna L, Shaik J, Radaelli E, De Antonellis P, Tarantino D, Pirolli A, Ragno R, Zollo M, Stunnenberg HG, Mai A, Altucci L}, title={RIP1-HAT1-SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer}, date={2018 Jun 15}, journal={Clin Cancer Res (ISSN: 1078-0432print, 1078-0432linking)}, year={2018}, fullvolume={219}, volume={219}, pages={2886--2900}, url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052287980&doi=10.1158%2f1078-0432.CCR-17-3081&partnerID=40&md5=40eb37bac795274af9b9ca4d6a11c13c}, abstract={Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes. Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models. Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo. Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. ©2018 American Association for Cancer Research.}, keywords={12 Dimethylbenz[a]anthracene, Caspase 8, Histone Acetyltransferase, Hydrolase Inhibitor, Mc 2494, Phosphotransferase, Rip1 Kinase, Rip3 Kinase, Sirtuin 1, Unclassified Drug, Animal Experiment, Animal Model, Apoptosis, Article, Breast Cancer, Cancer Model, Cancer Prevention, Cancer Therapy, Cell Death, Complex Formation, Controlled Study, Enzymatic Assay, Ex Vivo Study, Female, Flow Cytometry, Genetic Transfection, Human, Human Cell, Immunoprecipitation, In Vitro Study, In Vivo Study, Infant, Malignant Neoplasm, Mass Spectrometry, Mouse, Mouse Model, Mutagenesis, Nonhuman, Priority Journal, Protein Acetylation, Protein Protein Interaction, Transcriptomics, Tumor Xenograft, }, references={Galluzzi, L., Kroemer, G., Secondary necrosis: Accidental no more (2017) Trends Cancer, 3, pp. 1- Galluzzi, L., 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New APEH inhibitors having triazole-based structures have been recently reported. On this basis we have screened a set of click-generated cyclic peptides, previously investigated for peptide conformational stability studies, as possible novel enzyme inhibitors. We have found a clicked peptide, NHB3.3, that inhibits APEH activity and structure-activity studies highlighted that APEH inhibition is mediated by the spatial organization of the triazole ring and by its orientation and distance from the peptide scaffold, whose structural integrity, in turn, also plays a relevant role. In conclusion, our findings confirm that 1,2,3 triazoles are privileged pharmacophores for specific serine protease inhibitors and provide structural insights exploitable for modulating their inhibition activity. © The Royal Society of Chemistry 2015.}, keywords={Amino Acids, Diagnosis, Enzyme Inhibition, Nitrogen Compounds, Proteins, Acetylated Amino Acids, Conformational Stabilities, Inhibition Activity, Serine Protease Inhibitor, Spatial Organization, Structural Insights, Structure Activity Study, Therapeutic Targets, Peptides, Click-Chemistry, ?-Hairpin Peptide, Serine-Protease, }, references={Szeltner, Z., Rea, D., Juhász, T., Renner, V., Fülöp, V., Polgár, L., (2004) J. Mol. Biol., 340, p. 62 Rea, D., Fülöp, V., (2006) Cell Biochem. Biophys., 44, p. 349 Sharma, K.K., Ortwerth, B.J., (1993) Eur. J. 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Chem., 67, p. 3057 Li, H., Aneja, R., Chaiken, I., (2013) Molecules, 18, p. 9797}, document_type={Journal Article, }, affiliation={Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Via Mezzocannone 16Naples, Italy CIRPEB-University of Naples Federico IINaples, Italy Institute of Biosciensces and BioResources, National Research Council (CNR-IBBR)Naples, Italy Istituto di Biostrutture e Bioimmagini Istituto di Bioscienze e Biorisorse}, ibbaffiliation={1}, } @article{IBB_ID_53236, author={Miceli M, Dell'Aversana C, Russo R, Rega C, Cupelli L, Ruvo M, Altucci L, Chambery A}, title={Secretome profiling of cytokines and growth factors reveals that neuro-glial differentiation is associated with the down-regulation of Chemokine Ligand 2 (MCP-1/CCL2) in amniotic fluid derived-mesenchymal progenitor cells}, date={2016}, journal={Proteomics (ISSN: 1615-9853)}, year={2016}, fullvolume={423}, volume={423}, pages={674--688}, url={https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84958599044&partnerID=40&md5=d2fc9d5afd628336694404863fad71c4}, abstract={Secreted cytokines and growth factors play a key role in the modulation of stem cell proliferation, differentiation and survival. To investigate the interplay between the changes in their expression levels, we used the newly characterized human amniotic fluid derived-mesenchymal progenitor MePR-2B cell line differentiated to a neuro-glial phenotype and exploited the very high sensitivity and versatility of magnetic beads-based immunoassays. We found that a