Design, structural and biological characterization of a VEGF inhibitor β-hairpin-constrained peptide

• VEGF is an important therapeutic target for angiogenesis-dependent diseases.
• A novel VEGF antagonist peptide was designed by a structure-based approach.
• Peptide structure was analyzed in solution by NMR techniques.
• The peptide inhibits VEGF receptor signaling in endothelial cells.
• The peptide inhibits proliferation and survival of VEGF-stimulated endothelial cells.

The design, structural and biological characterization of a novel VEGF inhibitor peptide is described. The peptide was designed on the β5–β6 hairpin region of Placenta Growth Factor. NMR studies showed that the peptide assumes in solution a β-hairpin conformation similarly to the corresponding region of the natural ligand. In vitro experiments on endothelial cells demonstrated that the peptide is able to inhibit VEGF biological activity. This molecule represents a novel molecular entity to modulate VEGF activity and with potential application in therapy and diagnosis of angiogenesis-dependent diseases.

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