Ma, J, Cao, Q, McLeod, SM et al. (4 more authors) (2015) Target-Based Whole-Cell Screening by 1HNMR Spectroscopy. Angewandte Chemie - International Edition, 54 (16). 4764 - 4767. ISSN 1433-7851
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 μM, 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
Keywords: | Drug discovery; in vivo methods; New Delhi metallo-β-lactamase; NMR spectroscopy; Whole-cell screening |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Sep 2015 15:42 |
Last Modified: | 29 Mar 2018 03:37 |
Published Version: | http://dx.doi.org/10.1002/anie.201410701 |
Status: | Published |
Publisher: | Wiley-VCH Verlag |
Identification Number: | 10.1002/anie.201410701 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87490 |