Novel short peptides isolated from phage display library inhibit vascular endothelial growth factor activity

Erdag B., BALCIOGLU K. B. , Kumbasar A. , CELIKBICAK O., ZEDER-LUTZ G., ALTSCHUH D., ...More

MOLECULAR BIOTECHNOLOGY, vol.35, no.1, pp.51-63, 2007 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2007
  • Doi Number: 10.1385/mb:35:1:51
  • Page Numbers: pp.51-63


Signal transduction through the vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) pathway has a pivotal importance in angiogenesis, and has therefore become a prime target in antitumor therapy. In search for peptides antagonizing VEGF binding to its receptors, we screened a random heptamer library displayed on phage for peptides that bind the whole VEGF(165) molecule and inhibit VEGF dependent human umbilical vein endothelial cell (HUVEC) proliferation. Two selected peptides with sequences WHLPFKC and WHKPFRF were synthesized. Biacore and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis indicated that these peptides bind the VEGF homodimer in a concentration dependent manner, with micromolar affinity, and with a 2:1 peptide:VEGF stoichiometry. They inhibited HUVEC proliferation in vitro by 77 and 55%, respectively. Taken together, our results indicate that these peptides could be potent inhibitors of angiogenesis. Furthermore, we show that the peptide-VEGF binding properties can be quantified, a prerequisite for the further of binders.