Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging

Bioorg Med Chem Lett. 2011 Apr 1;21(7):2116-20. doi: 10.1016/j.bmcl.2011.01.133. Epub 2011 Feb 23.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cyclization
  • Disulfides / chemistry*
  • Fluorescent Dyes / chemistry*
  • Integrins / chemistry*
  • Oligopeptides / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Near-Infrared


  • Disulfides
  • Fluorescent Dyes
  • Integrins
  • Oligopeptides
  • arginyl-glycyl-aspartic acid