A Vinyl Sulfone-Based Fluorogenic Probe Capable of Selective Labeling of PHGDH in Live Mammalian Cells

Sijun Pan, Se Young Jang, Si Si Liew, Jiaqi Fu, Danyang Wang, Jun Seok Lee, Shao Q. Yao

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Chemical probes are powerful tools for interrogating small molecule-target interactions. With additional fluorescence Turn-ON functionality, such probes might enable direct measurements of target engagement in live mammalian cells. DNS-pE (and its terminal alkyne-containing version DNS-pE2) is the first small molecule that can selectively label endogenous 3-phosphoglycerate dehydrogenase (PHGDH) from various mammalian cells. Endowed with an electrophilic vinyl sulfone moiety that possesses fluorescence-quenching properties, DNS-pE/DNS-pE2 became highly fluorescent only upon irreversible covalent modification of PHGDH. With an inhibitory property (in vitro Ki=7.4 μm) comparable to that of known PHGDH inhibitors, our probes thus offer a promising approach to simultaneously image endogenous PHGDH activities and study its target engagement in live-cell settings.

Original languageEnglish
Pages (from-to)579-583
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number2
DOIs
Publication statusPublished - 2018 Jan 8
Externally publishedYes

Keywords

  • chemical proteomics
  • fluorescent probes
  • inhibitors
  • live-cell imaging
  • PHGDH

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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