Development of an activity-based chemiluminogenic probe for γ-glutamylcyclotransferase

Org Biomol Chem. 2023 Jul 26;21(29):5977-5984. doi: 10.1039/d3ob00655g.

Abstract

While γ-glutamylcyclotransferase (GGCT) has been implicated in cancer-cell proliferation, the role of GGCT enzymatic activity in the regulation of cancer-cell growth remains unclear. Toward further understanding of GGCT in vivo, here we report a novel cell-permeable chemiluminogenic probe "MAM-LISA-103" that detects intracellular GGCT activity and apply it to in vivo imaging. We first developed a chemiluminogenic probe LISA-103, which simply and sensitively detects the enzymatic activity of recombinant GGCT through chemiluminescence. We then designed the cell-permeable GGCT probe MAM-LISA-103 and applied it to several biological experiments. MAM-LISA-103 successfully detected the intracellular GGCT activity in GGCT-overexpressing NIH-3T3 cells. Moreover, MAM-LISA-103 demonstrated tumor-imaging ability when administered to a xenograft model using immunocompromised mice inoculated with MCF7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorescent Dyes / chemistry
  • Humans
  • MCF-7 Cells
  • Mice
  • gamma-Glutamylcyclotransferase* / chemistry

Substances

  • gamma-Glutamylcyclotransferase
  • Fluorescent Dyes