The Inorganic Perspective of VEGF: Interactions of Cu2 + with Peptides Encompassing a Recognition Domain of the VEGF Receptor

• Chemical-physical study of VEGF (Vascular endotelial growth factor) peptide fragments
• A VEGF165 fragment displays a binding high affinity for copper(II) ions
• The VEGF73-101 shows a significant antagonist activity in respect to VEGF protein
• The VEGF73-101 is involved in the pathway of kinase cascade through apoptosis mechanism.
• The peptide should favored the intracellular increase of metal ion toxicity

The vascular endothelial growth factor A (VEGF-A) is a potent angiogenic factor, its activity may be influenced by the presence of copper(II) ions. To mimic the interaction between copper(II) and VEGF (Vascular Endotelial Growth Factor), the N- and C-terminally blocked peptide fragments VEGF73-101 and VEGF84-101, owing to VEGF165 protein, have been synthesized. These protein domains represent a specific recognition site with the VEGF receptor (VEGFR). Copper(II) complexes with VEGF73-101 and VEGF84-101 were investigated by means of potentiometry and UV-Vis, ESI-MS, CD, EPR spectroscopic methods. Both peptides have three histidine residues and display a binding high affinity for copper(II) ions. The proliferative activity of the peptides in the absence and presence of copper(II) ions as well as of VEGF-165 protein was also tested on HUVEC cells (Human Umbilical Vein Endothelial Cells). The VEGF73-101 showed a dose-dependent anti-proliferative activity, while the shorter peptide VEGF84-101 did not affect HUVEC proliferation, both in the presence and in the absence of VEGF.

VEGF (vascular endotelial growth factor) peptide fragments strongly bind copper(II) ion. The peptide shows a dose-dependent anti-proliferative activity in HUVEC cell (Human Umbilical Vein Endothelial Cells), both in the presence and in the absence of VEGF. Besides the metal ion influences the anti-proliferative activity of the peptide.Figure optionsDownload as PowerPoint slide