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

Berrin Erdag*, Koray B. Balcioglu, Asli Kumbasar, Omur Celikbicak, Gabrielle Zeder-Lutz, Danièle Altschuh, Bekir Salih, Kemal Baysal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)51-63
Number of pages13
JournalMolecular Biotechnology
Issue number1
Publication statusPublished - Jan 2007
Externally publishedYes


This work was partially supported by a grant from TUBITAK Health Science Research Group project (SBAG-MAM-1, 102S005). We thank National Cancer Institute, Biological Resources Branch (Rockville, MD) for the generous gift of rhVEGF165 and Dr. Sandor Pongor, International Center for Genetic Engineering and Biotechnol- ogy (ICGEB) Trieste, Italy for the synthesis of the YHSSFQA peptide, Dr. Kemal Kazan for his comments on this manuscript and Aydin Bahar for technical assistance.

FundersFunder number
TUBITAK Health Science Research Group102S005, SBAG-MAM-1


    • Angiogenesis
    • HUVEC
    • Peptide
    • Phage display
    • Vascular endothelial growth factor


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