The Inorganic Perspective of VEGF: Interactions of Cu(2+) with Peptides Encompassing a Recognition Domain of the VEGF Receptor

J Inorg Biochem. 2016 Jun:159:149-58. doi: 10.1016/j.jinorgbio.2016.03.004. Epub 2016 Mar 15.

Abstract

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.

Keywords: HUVEC; VEGF; angiogenesis; copper; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects*
  • Copper* / chemistry
  • Copper* / pharmacology
  • Dose-Response Relationship, Drug
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Protein Domains
  • Receptors, Vascular Endothelial Growth Factor* / chemistry
  • Receptors, Vascular Endothelial Growth Factor* / metabolism
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Peptides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Copper
  • Receptors, Vascular Endothelial Growth Factor