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Chemical Modification for Proteolytic Stabilization of the Selective alphavbeta3 Integrin RGDechi Peptide: in Vitro and in Vivo Activities on Malignant Melanoma Cells (239 visite) (PDF privato 67 visite)

Comegna D, Zannetti A, Del Gatto A, De Paola I, Russo L, Di Gaetano S, Liguoro A, Capasso D, Saviano M, Zaccaro L

J Med Chem (ISSN: 1520-4804electronic, 0022-2623linking, 0022-2623print), 2017 Dec 14; 60(23): 9874-9884.

Tipo di articolo: Journal Article,

Impact factor: 5.207

Impact factor a 5 anni: 5.18


Parole chiave: Animals, Antineoplastic Agents, Chemistry, Pharmacology, Cell Adhesion, Drug Effects, Cell Line, Tumor, Humans, Integrin Alphavbeta3, Metabolism, Melanoma, Diagnostic Imaging, Drug Therapy, Nude, Molecular Docking Simulation, Optical Imaging, Methods, Peptides, Wound Healing,

Url: Non disponibile.

Herein, we report the synthesis and biological characterization of the new peptide psiRGDechi as the first step toward novel-targeted theranostics in melanoma. This pseudopeptide is designed from our previously reported RGDechi peptide, known to bind selectively alphavbeta3 integrin, and differs for a modified amide bond at the main protease cleavage site. This chemical modification drastically reduces the enzymatic degradation in serum, compared to its parental peptide, resulting in an overall magnification of the biological activity on a highly expressing alphavbeta3 human metastatic melanoma cell line. Selective inhibition of cell adhesion, wound healing, and invasion are demonstrated; near-infrared fluorescent psiRGDechi derivative is able to detect alphavbeta3 integrin in human melanoma xenografts in a selective fashion. More, molecular docking studies confirm that psiRGDechi recognizes the receptor similarly to RGDechi. All these findings pave the way for the future employment of this novel peptide as promising targeting probe and therapeutic agent in melanoma disease.
*** IBB - CNR ***

Institute of Biostructures and Bioimaging-CNR , Via Mezzocannone 16, 80134 Naples, Italy., Institute of Biostructures and Bioimaging-CNR , Via De Amicis 95, 80145 Naples, Italy., Interdepartmental Center of Bioactive Peptide, University of Naples Federico II , Via Mezzocannone 16, 80134 Naples, Italy., Department of Environmental, Biological and Pharmaceutical Science and Technology, University of Campania Luigi Vanvitelli , via Vivaldi 43, 81100 Caserta, Italy., Department of Pharmacy, University of Naples Federico II , Via Mezzocannone 16, 80134 Naples, Italy., Institute of Crystallography-CNR , Via Amendola 122/O, 70126 Bari, Italy.,
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Squeglia F, Ruggiero A, Berisio R
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Sciacca MFM, Romanucci V, Zarrelli A, Monaco I, Lolicato F, Spinella N, Galati C, Grasso G, D'Urso L, Romeo M, Diomede L, Salmona M, Bongiorno C, Di Fabio G, La Rosa C, Milardi D
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Improta R, Santoro F, Blancafort L
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Molinaro A, Holst O, Lorenzo FD, Callaghan M, Nurisso A, D'Errico G, Zamyatina A, Peri F, Berisio R, Jerala R, Jiménez-Barbero J, Silipo A, Martín-Santamarí S
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Bellia F, Rizzarelli E, Vecchio G
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Accardo A, Ringhieri P, Tesauro D, Morelli G
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Improta R
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Avitabile C, Moggio L, D'Andrea LD, Pedone C, Romanelli A
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Berisio R, Baram D, Keinan E
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Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD
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Ogawa R, Pacelli R, Espey MG, Miranda KM, Friedman N, Kim SM, Cox G, Mitchell JB, Wink DA, Russo A
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Impellizzeri G, Pappalardo G, D'Alessandro F, Rizzarelli E, Saviano M, Iacovino R, Benedetti E, Pedone C
Erratum: Solid state and solution conformation of 6-{4-[N-tert- butoxycarbonyl-N-(N'-ethyl)propanamide]imidazolyl}-6- deoxycyclomaltoheptaose: Evidence of self-inclusion of the boc group within the β-cyclodextrin cavity (European Journal of Organic Chemistry (2000) (1065-1076)) (112 visite)
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14 Records (12 escludendo Abstract e Conferenze).
Impact factor totale: 91.128 (85.819 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 91.957 (86.119 escludendo Abstract e Conferenze).







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