Synthesis and evaluation of new NIR-fluorescent probes for cathepsin B: ICT versus FRET as a turn-ON mode-of-action

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2453-8. doi: 10.1016/j.bmcl.2014.04.022. Epub 2014 Apr 16.

Abstract

Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix. Consequently, this protease has been attracting significant attention in cancer research, and many imaging probes targeting its activity have been developed. Here, we describe the design, synthesis and evaluation of two novel near infrared (NIR) fluorescent probes for detection of cathepsin B activity with different turn-ON mechanisms. One probe is based on an ICT activation mechanism of a donor-two-acceptor π-electron dye system, while the other is based on the FRET mechanism obtained by a fluorescent dye and a quencher. The two probes exhibit significant fluorescent turn-ON response upon cleavage by cathepsin B. The NIR fluorescence of the ICT probe in its OFF state was significantly lower than that of the FRET-based probe. This effect results in a higher signal-to-noise ratio and consequently increased sensitivity and better image contrast.

Keywords: Cathepsin B; Cyanine dyes; Fluorescent probes; Near infrared fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin B / analysis*
  • Cathepsin B / metabolism
  • Fluorescence Resonance Energy Transfer*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Humans
  • Infrared Rays
  • Molecular Imaging*
  • Molecular Structure

Substances

  • Fluorescent Dyes
  • Cathepsin B