The Inorganic Perspective of VEGF: Interactions of Cu2 + with Peptides Encompassing a Recognition Domain of the VEGF Receptor
Giulia Grasso, Anna Maria Santoro, Antonio Magrì, Diego La Mendola, Marianna Flora Tomasello, Stefania Zimbone, Enrico Rizzarelli
Journal of Inorganic Biochemistry
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.
Circular dichroism, Ligand binding, Secondary structure, Inorganic chemistry, Biochemistry