Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling.

ABSTRACT: Diverse strategies have been explored to mimic the surface displayed by an α-helical segment of a protein, with the goal of creating inhibitors of helix-mediated protein-protein interactions. Many recognition surfaces on proteins, however, are topologically more complex and less regular than a single α-helix. We describe efforts to develop peptidic foldamers that bind to the irregular receptor-recognition surface of vascular endothelial growth factor (VEGF). Our approach begins with a 19-residue α-peptide previously reported by Fairbrother et al. (Biochemistry 1998, 37, 17754) to bind to this surface on VEGF. Systematic evaluation of α→β replacements throughout this 19-mer sequence enabled us to identify homologues that contain up to ~30% β residues, retain significant affinity for VEGF, a

SUBMITTER: Haase HS 

PROVIDER: S-EPMC3551614 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature