1. A Vinyl Sulfone-Based Fluorogenic Probe Capable of Selective Labeling of PHGDH in Live Mammalian Cells.
- Author
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Pan, Sijun, Jang, Se‐Young, Liew, Si Si, Fu, Jiaqi, Wang, Danyang, Lee, Jun‐Seok, and Yao, Shao Q.
- Subjects
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SULFONES , *MOLECULAR structure , *CHEMICAL synthesis , *FLUORESCENCE , *MACROMOLECULAR synthesis - 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 μ m) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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