Structural investigation of the VEGF receptor interaction with a helical antagonist peptide‡. (19th February 2013)

• Record Type: Journal Article
• Authors: Diana, Donatella; Di Stasi, Rossella; De Rosa, Lucia; Isernia, Carla; D'Andrea, Luca D.; Fattorusso, Roberto
• Other Names: Morelli Giancarlo guestEditor.
• Is Part Of: Journal of peptide science. Volume 19:Number 4(2013:Apr.)
• Page Start: 214
• Page End: 219
• Publication Date: 2013-02-19
• Subjects: VEGF -- angiogenesis -- NMR -- peptide -- interactions; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2480
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Angiogenesis is mainly regulated by the vascular endothelial growth factor (VEGF), a mitogen specific for endothelial cells, which binds two tyrosine kinase receptors, VEGFR1 and VEGFR2, on the surface of endothelial cells. Molecules targeting VEGF receptors are attractive to pharmacologically treat diseases associated with angiogenesis or to be used as probes in angiogenesis imaging. Recently, we reported a designed peptide targeting VEGF receptors and able to inhibit the VEGF‐angiogenic response in vitro and in vivo . In this study, we employed NMR and molecular modeling methodology to investigate the molecular determinants of the interaction peptide‐receptor. In particular, the peptide binding site on VEGFR1 domain 2 and the residues involved in receptor recognition have been determined. These results provide significant information to develop a new class of molecules able to recognize the VEGF receptors overexpressed in pathological angiogenesis. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. Abstract : Recently, the designed peptide, named MA, has been demonstrated to assume in water a well‐defined helical conformation, to bind to vascular endothelial growth factor (VEGF) receptors, and to inhibit the VEGF‐induced capillary formation and tumor growth. In this study, we identified, combining solution NMR studies and molecular modeling, the molecular determinants of the binding surface between peptide MA and VEGFR1D2 . Particularly, the peptide binding site on VEGFR1D2 and peptide residues involved in receptor recognition have been determined.