TY - JOUR
T1 - Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging
AU - Ye, Yunpeng
AU - Xu, Baogang
AU - Nikiforovich, Gregory V.
AU - Bloch, Sharon
AU - Achilefu, Samuel
N1 - Funding Information:
This work was supported in part by the US National Institutes of Health grants from the NIBIB ( R01EB00811 and R01 EB007276 ) and the NCI ( R33 CA123537 and R01CA109754 ).
PY - 2011/4/1
Y1 - 2011/4/1
N2 - 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 α vβ3 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.
AB - 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 α vβ3 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.
KW - Disulfide-based cyclization
KW - Integrin αβ binding
KW - Near-infrared fluorescent probe
KW - Optical imaging
KW - RGD peptide
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U2 - 10.1016/j.bmcl.2011.01.133
DO - 10.1016/j.bmcl.2011.01.133
M3 - Article
C2 - 21349709
AN - SCOPUS:79952487388
SN - 0960-894X
VL - 21
SP - 2116
EP - 2120
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 7
ER -