A molecular dynamics study of an endostatin-derived peptide with antiangiogenic activity and of its mutants

• Published in: Chemical physics letters Vol. 455; no. 4; pp. 311 - 315
• Main Authors: Pieraccini, Stefano, Saladino, Giorgio, Sironi, Maurizio, Francescato, Pierangelo, Cattaneo, Maria G., Vicentini, Lucia M., Speranza, Giovanna, Manitto, Paolo
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.04.2008
• ISSN: 0009-2614; 1873-4448
• DOI: 10.1016/j.cplett.2008.02.106

Point mutation in peptides may influence their structure and biological activity. Molecular dynamics is an useful tool for exploring their effects. Human endostatin is an endogenous angiogenesis inhibitor, and its ability to modulate tumors vascularization is of great therapeutic interest. The antiangiogenic activity is conserved also in some of its synthetic fragments. Fragment 6-49, in particular, is even more active than full length protein. It covers an endostatin region which shows two phenylalanines unusually exposed on the surface. The effect of the mutation of these residues on fragment 6-49 structure and activity are discussed and compared to those of a similar mutation in full length endostatin. A hypothesis on the fragment active epitope is supported by data from molecular dynamics simulations.