Synthesis and Solution Conformation of Cyclo[RGDRGD]: A Cyclic Peptide with Selectivity for the αVβ3 Receptor

摘要: Three peptides, cyclo[RGDRGD], cyclo[RGDRGd] (d = d-Asp), and the linear sequence RGDRGD, were prepared via solid phase syntheses. These tested in binding assays based upon αIIb/β3-fibrinogen αVβ3-vitronectin interactions found to be selective for αVβ3 integrin. The is important bone regeneration, hence compounds also an osteoclast regeneration assay; all three compounds, cyclo[RGDRGd], showed modest activities. Molecular modeling, NMR, CD studies undertaken elucidate conformational preferences of cyclo[RGDRGD] aqueous solutions. Results from these strongly suggest that molecule tends adopt a type I β-turn conformation with relatively short distance between Asp Arg side chains. observations are harmony first correlations made selectivity solution peptide ligand (Pfaff, M.; et al. J. Biol. Chem. 1994, 269, 20233).