title: The Inorganic Perspective of VEGF: Interactions of Cu(2+) with Peptides Encompassing a Recognition Domain of the VEGF Receptor.
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.
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy. Electronic address: giulia.grasso@cnr.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Grasso
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Santoro
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Magrì
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano, 6-56126 Pisa, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: La Mendola
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy.
authors.forename: Marianna Flora
authors.initials: MF
authors.lastname: Tomasello
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zimbone
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Catania, Via P. Gaifami, 18 -95126 Catania, Italy; Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria, 6-95126 Catania, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D000072417:Protein Domains; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010455:Peptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003300:Copper; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: HUVEC; VEGF; angiogenesis; copper; peptides