A Cyclopropene Electrophile that Targets Glutathione S-Transferase Omega-1 in Cells

Angew Chem Int Ed Engl. 2019 Aug 19;58(34):11918-11922. doi: 10.1002/anie.201907520. Epub 2019 Jul 26.

Abstract

Cyclopropenes are an important new addition to the portfolio of functional groups that can be used for bioorthogonal couplings. The inert nature of these highly strained compounds in complex biological systems is almost counterintuitive given their established electrophilic properties in organic synthesis. Here we provide the first demonstration of a cyclopropene that is capable of direct conjugation to protein targets in cells and show that this compound preferentially alkylates the active site cysteine of glutathione S-transferase omega-1 (GSTO1).

Keywords: GSTO1 inhibition; bioorthogonal chemistry; chemical proteomics; cyclopropene; electrophiles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cyclopropanes / pharmacology*
  • Cysteine / chemistry
  • Cysteine / metabolism*
  • Glutathione / chemistry
  • Glutathione / metabolism*
  • Glutathione Transferase / antagonists & inhibitors*
  • Glutathione Transferase / metabolism*
  • HCT116 Cells
  • Humans

Substances

  • Cyclopropanes
  • cyclopropene
  • GSTO1 protein, human
  • Glutathione Transferase
  • Glutathione
  • Cysteine