title: Parallel solid-phase synthesis of a small library of linear and hydrocarbon-bridged analogues of VEGF(81-91): potential biological tools for studying the VEGF/VEGFR-1 interaction.
abstract: The design, synthesis and binding affinity for VEGFR-1 receptors of a small library of linear and cyclic analogues of the VEGF(81-91) fragment are described. Cyclic 11- and 10-mer peptide derivatives were prepared using parallel solid-phase protocols. The formation of hydrocarbon alkene-bridged cyclic peptides was achieved through optimized ring-closing metathesis reactions from linear derivatives with conveniently located allylGly residues. Alkane-bridged analogues were successfully obtained by ulterior on-resin hydrogenation. Binding assays showed that some of these compounds were able to compete with labeled VEGF for interaction with the VEGFR-1 receptor. Several peptide derivatives, 2, 7 and 8, showed modest but significant binding affinity, indicating that the designed peptide could mimic the VEGF(81-91) fragment and therefore disrupt the VEGF/VEGFR-1 interaction. This fact opens the way for using these peptides as the starting point for biological/pharmacological tools to deeply investigate this protein-protein system.
authors.affiliation: Instituto de Química Médica, CSIC. C/Juan de la Cierva, 3. 28006 Madrid, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: García-Aranda
authors.forename: Patricia
authors.initials: P
authors.lastname: Marrero
authors.forename: Benoit
authors.initials: B
authors.lastname: Gautier
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martín-Martínez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Inguimbert
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-López
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Jiménez
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez de Vega
mesh_terms: D000595:Amino Acid Sequence; D006838:Hydrocarbons / Q000737:chemistry*; D006865:Hydrogenation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D006838:Hydrocarbons; D010455:Peptides; D054852:Small Molecule Libraries; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1