Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging |
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Authors: | Ye Yunpeng Xu Baogang Nikiforovich Gregory V Bloch Sharon Achilefu Samuel |
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Institution: | a Department of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA b Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA |
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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 αvβ3 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 αvβ3 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 αvβ3 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. |
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Keywords: | Disulfide-based cyclization RGD peptide Integrin αvβ3 binding Near-infrared fluorescent probe Optical imaging |
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