Design and Synthesis of C-Terminal Modified Cyclic Peptides as VEGFR1 Antagonists

Molecules

Lei Wang¹  Nathalie Gagey-Eilstein¹  Sylvain Broussy¹  Marie Reille-Seroussi¹  Florent Huguenot¹  Michel Vidal¹  Wang-Qing Liu¹ 

[1] UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 avenue de l’observatoire, Paris 75006, France; E-Mails:

关键词: VEGF;    VEGFR;    angiogenesis;    cyclic peptides;   

DOI  :  10.3390/molecules191015391

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.