Novel Inhibitors of E. coli RecA ATPase Activity
Jonathan Z Sexton*, 1, Tim J Wigle2, Qingping He1, Mark A Hughes1, Ginger R Smith1, Scott F Singleton2, Alfred L Williams1, Li-An Yeh1
Identifiers and Pagination:Year: 2010
First Page: 34
Last Page: 42
Publisher Id: CCGTM-4-34
Article History:Received Date: 23/10/2009
Revision Received Date: 07/12/2009
Acceptance Date: 12/12/2009
Electronic publication date: 26/5/2010
Collection year: 2010
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
The bacterial RecA protein has been implicated as a bacterial drug target not as an antimicrobial target, but as an adjuvant target with the potential to suppress the mechanism by which bacteria gain drug resistance. In order to identify small molecules that inhibit RecA/ssDNA nucleoprotein filament formation, we have adapted the phosphomolybdate-blue ATPase assay for high throughput screening to determine RecA ATPase activity against a library of 33,600 compounds, which is a selected representation of diverse structure of 350,000. Four distinct chemotypes were represented among the 40 validated hits. SAR and further chemical synthesis is underway to optimize this set of inhibitors to be used as antimicrobial adjuvant agents.