title: Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging.
abstract: We synthesized disulfide-based cyclic RGD pentapeptides bearing a near-infrared fluorescent dye (cypate), represented by cypate-c(CRGDC) (1) for integrin-targeted optical imaging. These compounds were compared with the traditional lactam-based cyclic RGD counterpart, cypate-c(RGDfK) (2). Molecular modeling suggests that the binding affinity of 2 to integrin α(v)β(3) is an order of magnitude higher than that of 1. This was confirmed experimentally, which further showed that substitution of Gly with Pro, Val and Tyr in 1 remarkably hampered the α(v)β(3) binding. Interestingly, cell microscopy with A549 cells showed that 1 exhibited higher cellular staining than 2. These results indicate that factors other than receptor binding affinity to α(v)β(3) dimeric proteins mediate cellular uptake. Consequently, 1 and its analogs may serve as valuable molecular probes for investigating the selectivity and specificity of integrin targeting by optical imaging.
authors.affiliation: Department of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St Louis, MO 63110, USA.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.forename: Baogang
authors.initials: B
authors.lastname: Xu
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Nikiforovich
authors.forename: Sharon
authors.initials: S
authors.lastname: Bloch
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004220:Disulfides / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D016023:Integrins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D019265:Spectroscopy, Near-Infrared
chemical_list: D004220:Disulfides; D005456:Fluorescent Dyes; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid