Blocking angiogenesis is an attractive strategy to inhibit tumor growth, invasion, and metastasis. We describe here the structure and the biological action of a new cyclic peptide derived from vascular endothelial growth factor (VEGF). This 17-amino acid molecule designated cyclopeptidic vascular endothelial growth inhibitor (cyclo-VEGI, CBO-P11) encompasses residues 79-93 of VEGF which are involved in the interaction with VEGF receptor-2. In aqueous solution, cyclo-VEGI presents a propensity to adopt a helix conformation that was largely unexpected because only β-sheet structures or random coil conformations have been observed for macrocyclic peptides. Cyclo-VEGI inhibits binding of iodinated VEGF165 to endothelial cells, endothelial cells proliferation, migration, and signaling induced by VEGF165. This peptide also exhibits anti-angiogenic activity in vivo on the differentiated chicken chorioallantoic membrane. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival without side effects. Taken together, these results suggest that cyclo-VEGI is an attractive candidate for the development of novel angiogenesis inhibitor molecules useful for the treatment of cancer and other angiogenesis-related diseases.
Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor / L. Zilberberg, S. Shinkaruk, O. Lequin, B. Rousseau, M. Hagedorn, F. Costa, D. Caronzolo, M. Balke, X. Canron, O. Convert, G. Lain, K. Gionnet, M. Goncalves, M. Bayle, L. Bello, G. Chassaing, G. Deleris, A. Bikfalvi. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 278:37(2003), pp. 35564-35573.
|Titolo:||Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor|
|Parole Chiave:||Nuclear-magnetic-resonance; kinase domain receptor; common amino-acids; factor VEGF; in-vivo; crystal-structure; cell-proliferation; angstrom resolution; NMR-spectroscopy; binding site|
|Settore Scientifico Disciplinare:||Settore MED/27 - Neurochirurgia|
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M304435200|
|Appare nelle tipologie:||01 - Articolo su periodico|