Identification and localization of heparin-binding region of snake venom VEGF and its blocking of VEGF-A165.

Vascular endothelial growth factor (VEGF-A165) displays diverse effects through binding to its receptor, KDR (kinase domain-containing receptor). Heparan sulfate/heparin-like molecules greatly contribute to their interaction. Indeed, the mitogenic potency of VEGF-A165 lacking the C-terminal heparin-binding region is less than 1% compared with intact VEGF-A165. We previously found novel heparin-binding VEGFs, designated VEGF-F that specifically recognizes KDR in snake venoms. VEGF-Fs almost completely lack the C-terminal heparin-binding region compared with VEGF-A165, despite their heparin-binding potential. In this study, we attempted to identify the heparin-binding region of VEGF-F using synthetic peptides. We have demonstrated that the heparin-binding site of VEGF-F is located in its C-terminal region, particularly localized on the N-terminal portion of this region. Furthermore, a synthetic peptide of this region blocks the biological activity of VEGF-A165 in vitro and in vivo.