| Autor: |
Haase HS; Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA., Peterson-Kaufman KJ, Lan Levengood SK, Checco JW, Murphy WL, Gellman SH |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2012 May 09; Vol. 134 (18), pp. 7652-5. Date of Electronic Publication: 2012 May 01. |
| DOI: |
10.1021/ja302469a |
| Abstrakt: |
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, and display substantial resistance to proteolysis. These α/β-peptides can block VEGF-stimulated proliferation of human umbilical vein endothelial cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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