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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

43 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.",

keywords = "PHGDH, chemical proteomics, fluorescent probes, inhibitors, live-cell imaging",

author = "Sijun Pan and Jang, \{Se Young\} and Liew, \{Si Si\} and Jiaqi Fu and Danyang Wang and Lee, \{Jun Seok\} and Yao, \{Shao Q.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Wiley-VCH Verlag GmbH \& Co. KGaA, Weinheim",

year = "2018",

month = jan,

day = "8",

doi = "10.1002/anie.201710856",

language = "English",

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AU - Pan, Sijun

AU - Jang, Se Young

AU - Liew, Si Si

AU - Fu, Jiaqi

AU - Wang, Danyang

AU - Lee, Jun Seok

AU - Yao, Shao Q.

PY - 2018/1/8

Y1 - 2018/1/8

N2 - 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.

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.

KW - PHGDH

KW - chemical proteomics

KW - fluorescent probes

KW - inhibitors

KW - live-cell imaging

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U2 - 10.1002/anie.201710856

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JF - Angewandte Chemie - International Edition

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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