Potent inhibition of angiogenesis by D,L-peptides derived from vascular endothelial growth factor receptor 2
Piossek C., Thierauch K-H., Schneider-Mergener J., Volkmer-Engert R., Bachmann M., Korff T., Augustin H., Germeroth L.
<jats:title>Summary</jats:title><jats:p>Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and plays a central role in angiogenesis and vasculogenesis. Therefore, VEGF and its receptors VEGFR-1 and VEGFR-2 are prime targets for anti-angiogenic intervention which is thought to be one of the most promising approaches in cancer therapy. Recently, we have discovered a VEGFR-2-derived peptide (247RTELNVGIDFNWEYP261) representing a potential binding site to VEGF. Using the spot synthesis technique, systematic D-amino acid substitutional analyses of this peptide were conducted and the resulting D, L-peptides inhibit VEGF binding to VEGFR-2 at half maximal concentration of 30 nM.The serum-stable D, L-peptides further inhibited auto-phosphorylation of the VEGFR-2 at nanomolar concentrations. Testing of the peptides in a spheroid-based angiogenesis assay demonstrated a potent anti-angiogenic effect in vitro. The rational design of potent and stable anti-angiogenic peptide inhibitors from their parent receptors provides a feasible route to develop novel leads for anti-angiogenic medicines.</jats:p>