A Vinyl Sulfone‐Based Fluorogenic Probe Capable of Selective Labeling of PHGDH in Live Mammalian Cells |
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| Authors: | Dr. Sijun Pan Se‐Young Jang Si Si Liew Jiaqi Fu Danyang Wang Prof. Dr. Jun‐Seok Lee Prof. Dr. Shao Q. Yao |
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| Affiliation: | 1. Department of Chemistry, National University of Singapore, Singapore, Singapore;2. Molecular Recognition Research Center, Bio-Med Program of KIST-School UST, Korea Institute of Science & Technology, Seongbuk-gu, Seoul 136-791, Korea |
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| 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. |
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| Keywords: | chemical proteomics fluorescent probes inhibitors live-cell imaging PHGDH |
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