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

doi:10.1002/anie.201710856

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 journal › Article › peer-review

36 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 K_i=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 language	English
Pages (from-to)	579-583
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	57
Issue number	2
DOIs	https://doi.org/10.1002/anie.201710856
Publication status	Published - 2018 Jan 8
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

PHGDH
chemical proteomics
fluorescent probes
inhibitors
live-cell imaging

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.201710856

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

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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AU - Liew, Si Si

AU - Fu, Jiaqi

AU - Wang, Danyang

AU - Lee, Jun Seok

AU - Yao, Shao Q.

PY - 2018/1/8

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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