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Target‐Based Whole‐Cell Screening by 1 H NMR Spectroscopy
Author(s) -
Ma Junhe,
Cao Qing,
McLeod Sarah M.,
Ferguson Keith,
Gao Ning,
Breeze Alexander L.,
Hu Jun
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201410701
Subject(s) - escherichia coli , nuclear magnetic resonance spectroscopy , chemistry , cell , two dimensional nuclear magnetic resonance spectroscopy , fluorine 19 nmr , biochemistry , combinatorial chemistry , stereochemistry , gene
An NMR‐based approach marries the two traditional screening technologies (phenotypic and target‐based screening) to find compounds inhibiting a specific enzymatic reaction in bacterial cells. Building on a previous study in which it was demonstrated that hydrolytic decomposition of meropenem in living Escherichia coli cells carrying New Delhi metallo‐β‐lactamase subclass 1 (NDM‐1) can be monitored in real time by NMR spectroscopy, we designed a cell‐based NMR screening platform. A strong NDM‐1 inhibitor was identified with cellular IC 50 of 0.51 μ M , which is over 300‐fold more potent than captopril, a known NDM‐1 inhibitor. This new screening approach has great potential to be applied to targets in other cell types, such as mammalian cells, and to targets that are only stable or functionally competent in the cellular environment.