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- Title
Target-Based Whole-Cell Screening by <sup>1</sup>H NMR Spectroscopy.
- Authors
Ma, Junhe; Cao, Qing; McLeod, Sarah M.; Ferguson, Keith; Gao, Ning; Breeze, Alexander L.; Hu, Jun
- Abstract
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 IC50 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.
- Subjects
NUCLEAR magnetic resonance spectroscopy; BACTERIAL cells; ESCHERICHIA coli; DIMETHYL sulfoxide; ETHYLENEDIAMINETETRAACETIC acid
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 16, p4846
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201410701