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

Yunpeng Ye, Baogang Xu, Gregory V. Nikiforovich, Sharon Bloch, Samuel Achilefu

Research output: Contribution to journalArticle

14 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)2116-2120
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number7
DOIs
StatePublished - Apr 1 2011

Keywords

  • Disulfide-based cyclization
  • Integrin αβ binding
  • Near-infrared fluorescent probe
  • Optical imaging
  • RGD peptide

Fingerprint Dive into the research topics of 'Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging'. Together they form a unique fingerprint.

  • Cite this