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  • Title: Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor.
    Author: Zilberberg L, Shinkaruk S, Lequin O, Rousseau B, Hagedorn M, Costa F, Caronzolo D, Balke M, Canron X, Convert O, Laïn G, Gionnet K, Goncalvès M, Bayle M, Bello L, Chassaing G, Deleris G, Bikfalvi A.
    Journal: J Biol Chem; 2003 Sep 12; 278(37):35564-73. PubMed ID: 12837752.
    Abstract:
    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 beta-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.
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