Structure-based design of a bicyclic peptide antagonist of the vascular endothelial growth factor receptors

✍ Scribed by Victor Goncalves; Benoit Gautier; Christiane Garbay; Michel Vidal; Nicolas Inguimbert

• Book ID: 105360781
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 736 KB
• Volume: 14
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.965

✦ Synopsis

Abstract

Dysregulated angiogenesis is implicated in several pathologies, including cancer and age‐related macular degeneration. A potential antiangiogenic strategy consists in developing VEGF receptor ligands capable of preventing VEGF binding and the subsequent activation of these receptors. Herein, we describe the structure‐based design of a VEGF‐mimicking peptide, VG3F. This 25‐mer peptide was doubly cyclized, on‐resin, by formation of both a disulfide bridge and an intramolecular amide bond to constrain it to adopt a bioactive conformation. Tested on in vitro assays, VG3F was able to prevent VEGF binding to VEGF receptor 1 and inhibit both VEGF‐induced signal transduction and cell migration. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.