Disrupting VEGF-VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment.

摘要: The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis cancer, which moved us to search for peptide derivatives able block this protein–protein interaction. In a previous work we had described collection of linear 13-mer peptides specially designed adopt helical conformations (Ac-SSEEX5ARNX9AAX12N-NH2), as well the evaluation seven library components inhibition VEGF with Receptor 1 (VEGFR1). This study led discovery some new, quite potent inhibitors system. results found prompted extend other library. We describe here new selection from initial that allow identify VEGF-VEGFR1 inhibitors. Among them, sequence containing F, W, I residues at 5, 9, 12 positions, show very significant nanomolar IC50 value, competing receptor 1, VEGFR1 (Flt-1), could represent tool within therapeutic arsenal cancer detection therapy.