Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain "2"(301 views) Wang L, Coric P, Broussy S, Di Stasi R, Zhou L, D'Andrea LD, Ji L, Vidal M, Bouaziz S, Liu WQ
Eur J Med Chem (ISSN: 0223-5234linking, 1768-3254, 1768-3254electronic), 2019 May 1; 169: 65-75.
UMR 8038 CNRS, U 1268 INSERM, Faculte de Pharmacie de Paris, Universite Paris Descartes, Sorbonne Paris Cite, 4 Avenue de l'Observatoire, Paris, 75006, France.
UMR 8038 CNRS, Faculte de Pharmacie de Paris, Universite Paris Descartes, Sorbonne Paris Cite, 4 Avenue de l'Observatoire, Paris, 75006, France.
Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
UF biologie du medicament, toxicologie, hopital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, Paris, 75014, France.
References: Not available.
Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain "2"
Physiological and pathological angiogenesis is mainly regulated by the binding of the vascular endothelial growth factor (VEGF) to its receptors (VEGFRs). Antagonists of VEGFR are very attractive for the treatment of diseases related to excessive angiogenesis. Our previously designed C-terminal alkylated cyclic peptides [YKDEGLEE]-NHR (R=alkyl, arylalkyl) disrupt the interaction between VEGF and VEGFRs in biological assays. In this paper, we described the structural studies of the binding of one of these cyclic peptides named Peptide 3 to the VEGFR1 domain 2 (VEGFR1-D2). The molecular docking and NMR mapping identified the binding site on VEGFR1-D2. The anti-angiogenic effect of our peptide was evaluated by an experiment of VEGF-induced tube formation in two cell lines, retinal cell type RF6/A and vascular endothelial cell type HUVEC. Some new peptides were also synthesized and compared by an ELISA-based assay, in order to verify their ability to disrupt the formation of the complex VEGF-A/VEGFR1. In conclusion, the structural studies of Peptide 3 with VEGFR1-D2 will help the design of more efficient VEGFR antagonists. Moreover, Peptide 3, with improved receptor binding affinity, could be more suitable for VEGFR targeting bioimaging studies once labeled.
Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain "2"
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 * Human IgG1 antibodies suppress angiogenesis in a target-independent manner(682 views) Signal Transduct Target Ther (ISSN: 2059-3635print), 2016; 1: N/D-N/D. Impact Factor:0 ViewExport to BibTeXExport to EndNote
Santulli G, Cipolletta E, Sorriento D, Del Giudice C, Anastasio A, Monaco S, Maione AS, Condorelli G, Puca A, Trimarco B, Illario M, Iaccarino G * CaMK4 gene deletion induces hypertension(429 views) J Am Heart Assoc Journal Of The American Heart Association (ISSN: 2047-9980), 2012; 1(4): N/D-N/D. Impact Factor:2.882 ViewExport to BibTeXExport to EndNote
Ntziachristos V, Cuénod CA, Fournier L, Balvay D, Pradel C, Siauve N, Clement O, Jouannot E, Lucidarme O, Vecchio SD, Salvatore M, Law B, Tung C-H, Jain RK, Fukumura D, Munn LL, Brown EB, Schellenberger E, Montet X, Weissleder R, Clerck ND, Postnov A * Tumor Imaging(471 views) Textbook Of In Vivo Imaging In Vertebrates (ISSN: 9780-4700), 2007 Jul 16; 1: 277-309. Impact Factor:1.148 ViewExport to BibTeXExport to EndNote