title: Helical peptides from VEGF and Vammin hotspots for modulating the VEGF-VEGFR interaction.
abstract: The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal α-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorithm and prepared following peptide solid-phase synthetic protocols. Cyclic peptide derivatives were prepared on-resin from linear precursors with conveniently located Glu and Lys residues, by the formation of amide linkages. Conformational analysis, CD and NMR, showed that most synthesized peptides have a clear tendency to be structured as α-helices in solution. Some of the peptides were able to bind a VEGFR-1 receptor with moderate affinity. In addition to the described key residues (Phe17, Tyr21 and Tyr25), Val14 and Val20 seem to be relevant for affinity.
authors: Instituto de Química Médica, CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain.
authors: María Isabel
authors: MI
authors: García-Aranda
authors: Susana
authors: S
authors: González-López
authors: Clara María
authors: CM
authors: Santiveri
authors: Nathalie
authors: N
authors: Gagey-Eilstein
authors: Marie
authors: M
authors: Reille-Seroussi
authors: Mercedes
authors: M
authors: Martín-Martínez
authors: Nicolas
authors: N
authors: Inguimbert
authors: Michel
authors: M
authors: Vidal
authors: María Teresa
authors: MT
authors: García-López
authors: María Angeles
authors: MA
authors: Jiménez
authors: Rosario
authors: R
authors: González-Muñiz
authors: María Jesús
authors: MJ
authors: Pérez de Vega
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D014757:Viper Venoms; C519402:vammin protein, Vipera ammodytes ammodytes; D040262:Receptors, Vascular Endothelial Growth Factor