Characterization of a designed vascular endothelial growth factor receptor antagonist helical peptide with antiangiogenic activity in vivo

J Med Chem. 2011 Mar 10;54(5):1391-400. doi: 10.1021/jm101435r. Epub 2011 Jan 31.


Angiogenesis is a fundamental process underlining physiological and pathological conditions. It is mainly regulated by the vascular endothelial growth factor (VEGF) and its receptors, which are the main targets of molecules able to modulate the angiogenic response. Pharmaceutical therapies based on antiangiogenic drugs represent a promising approach for the treatment of several socially important diseases. We report the biological and structural characterization of a VEGF receptor binder peptide designed on the N-terminal helix of VEGF. The reported experimental evidence shows that the peptide assumes in water a well-defined helical conformation and indicates that this peptide is a VEGF receptor antagonist and possesses antiangiogenic biological activity. In particular, it inhibits VEGF stimulated endothelial cell proliferation, activation, and survival, as well as angiogenesis and tumor progression in vivo. This peptide is a candidate for the development of novel peptide-based drugs for the treatment of diseases associated with excessive VEGF-dependent angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Circular Dichroism
  • Endothelial Cells / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Protein Structure, Secondary
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / chemistry
  • Receptors, Vascular Endothelial Growth Factor / physiology
  • Signal Transduction / drug effects
  • Transplantation, Heterologous
  • Umbilical Veins / cytology
  • Water


  • Angiogenesis Inhibitors
  • Peptides
  • Water
  • Receptors, Vascular Endothelial Growth Factor