title: Design and synthesis of C-terminal modified cyclic peptides as VEGFR1 antagonists.
abstract: Previously designed cyclic peptide antagonist c[YYDEGLEE]-NH2 disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). It represents a promising tool in the fight against cancer and age-related macular degeneration. We described in this paper the optimization of the lead peptide by C-terminal modification. A new strategy for the synthesis of cyclic peptides is developed, improving the cyclisation efficiency. At 100 µM, several new peptides with an aromatic group flexibly linked at C-terminal end showed significantly increased receptor binding affinities in competition ELISA test. The most active peptide carrying a coumarin group may be a useful tool in anti-angiogenic biological studies.
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. lei.wang1@etu.parisdescartes.fr.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. nathalie.eilstein@parisdescartes.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gagey-Eilstein
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. sylvain.broussy@parisdescartes.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Broussy
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. marie.reille@etu.parisdescartes.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Reille-Seroussi
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. florent.huguenot@parisdescartes.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Huguenot
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. michel.vidal@parisdescartes.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l'observatoire, Paris 75006, France. wangqing.liu@parisdescartes.fr.
authors.forename: Wang-Qing
authors.initials: WQ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D010456:Peptides, Cyclic; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1