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

• Published in: Molecular biotechnology Vol. 35; no. 1; pp. 51 - 63
• Main Authors: ERDAG, Berrin, BALCIOGLU, Koray B, KUMBASAR, Asli, CELIKBICAK, Omur, ZEDER-LUTZ, Gabrielle, ALTSCHUH, Danièle, SALIH, Bekir, BAYSAL, Kemal
• Format: Journal Article
• Language: English
• Published: Totowa, NJ Humana Press 2007; Springer Nature B.V; Springer
• Subjects: Amino Acid Sequence; Angiogenesis Inhibitors; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Binders; Biochemistry; Biochemistry, Molecular Biology; Biological and medical sciences; Bioreactors; Biotechnology; Cell Proliferation; Cell Proliferation - drug effects; Cells; Cells, Cultured; Endothelial Cells; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Ionization; Life Sciences; Mass spectrometry; Oligopeptides; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptide Library; Peptides; Protein Binding; Proteins; Recombinant Proteins; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Signal transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Studies; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - pharmacology; Angiogenesis; Phage display; peptide; Vascular endothelium growth factor; Peptides; HUVEC; Inhibition; Vascular endothelial growth factor
• ISSN: 1073-6085; 1559-0305; 1073-6085
• DOI: 10.1385/MB:35:1:51

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 VEGF165 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 timeof- 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 optimization of binders.