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A method for identification of inhibitors of the phosphorylation reactions of bacterial response regulator proteins using 31P nuclear magnetic resonance spectroscopy

Hubbard, Julia A., MacLachlan, Lesley K., Johnson, Peter, Findlow, Stuart C., Ladds, Joanne C., Lewis, Ceri J., Carter, Paul S., Jones, Jo J. and Fosberry, Andrew P. (2001) A method for identification of inhibitors of the phosphorylation reactions of bacterial response regulator proteins using 31P nuclear magnetic resonance spectroscopy Analytical Biochemistry, 299, (1), pp. 31-36. (doi:10.1006/abio.2001.5365).

Record type: Article

Abstract

Bacterial response regulators are attractive targets for antibacterial drug development, yet random screening against these targets has failed as yet to identify chemicals that constitute viable leads. Alternative methods to provide leads for drug development based on identification and optimization of low affinity ligands from NMR screens have been described. However, leads from these processes still require verification in a bioassay, which is often problematic if compounds have unfavorable optical and solubility properties. A simple method, based on using NMR to observe the activity of the target, is described. It has the advantages of being able to characterize both low affinity leads and a wider selection of compounds in a structure activity relationships series, without the problems affecting a fluorescence assay. In this example we use 31P to monitor the turnover of a bacterial response regulator, but the generic approach could be applied to other nuclei and thus a range of biological systems.

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Published date: 1 December 2001

Identifiers

Local EPrints ID: 156635
URI: http://eprints.soton.ac.uk/id/eprint/156635
ISSN: 0003-2697
PURE UUID: 17b6c4b6-83b3-4c25-ad37-4e6bbd30c6fd

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Date deposited: 01 Jun 2010 12:11
Last modified: 18 Jul 2017 12:42

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Contributors

Author: Julia A. Hubbard
Author: Lesley K. MacLachlan
Author: Peter Johnson
Author: Stuart C. Findlow
Author: Joanne C. Ladds
Author: Ceri J. Lewis
Author: Paul S. Carter
Author: Jo J. Jones
Author: Andrew P. Fosberry

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