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

Eur J Med Chem. 2014 Feb 12:73:210-6. doi: 10.1016/j.ejmech.2013.12.016. Epub 2013 Dec 24.

Abstract

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.

Keywords: Angiogenesis; Drug design; NMR spectroscopy; Peptides; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Design*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Placenta Growth Factor
  • Pregnancy Proteins / chemistry*
  • Protein Conformation
  • Protein Engineering
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*

Substances

  • PGF protein, human
  • Peptides, Cyclic
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1