Novel Inhibitors of E. coli RecA ATPase Activity

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...

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Detalles Bibliográficos
Autores principales: Sexton, Jonathan Z, Wigle, Tim J, He, Qingping, Hughes, Mark A, Smith, Ginger R, Singleton, Scott F, Williams, Alfred L, Yeh, Li-An
Formato: Texto
Lenguaje:English
Publicado: Bentham Open 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905775/
https://www.ncbi.nlm.nih.gov/pubmed/20648224
http://dx.doi.org/10.2174/1875397301004010034
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author Sexton, Jonathan Z
Wigle, Tim J
He, Qingping
Hughes, Mark A
Smith, Ginger R
Singleton, Scott F
Williams, Alfred L
Yeh, Li-An
author_facet Sexton, Jonathan Z
Wigle, Tim J
He, Qingping
Hughes, Mark A
Smith, Ginger R
Singleton, Scott F
Williams, Alfred L
Yeh, Li-An
author_sort Sexton, Jonathan Z
collection PubMed
description 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.
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spelling pubmed-29057752010-07-20 Novel Inhibitors of E. coli RecA ATPase Activity Sexton, Jonathan Z Wigle, Tim J He, Qingping Hughes, Mark A Smith, Ginger R Singleton, Scott F Williams, Alfred L Yeh, Li-An Curr Chem Genomics Article 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. Bentham Open 2010-05-26 /pmc/articles/PMC2905775/ /pubmed/20648224 http://dx.doi.org/10.2174/1875397301004010034 Text en © Sexton et al.; Licensee Bentham Open. http://creativecommons.org/licenses/by-nc/3.0/ 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.
spellingShingle Article
Sexton, Jonathan Z
Wigle, Tim J
He, Qingping
Hughes, Mark A
Smith, Ginger R
Singleton, Scott F
Williams, Alfred L
Yeh, Li-An
Novel Inhibitors of E. coli RecA ATPase Activity
title Novel Inhibitors of E. coli RecA ATPase Activity
title_full Novel Inhibitors of E. coli RecA ATPase Activity
title_fullStr Novel Inhibitors of E. coli RecA ATPase Activity
title_full_unstemmed Novel Inhibitors of E. coli RecA ATPase Activity
title_short Novel Inhibitors of E. coli RecA ATPase Activity
title_sort novel inhibitors of e. coli reca atpase activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905775/
https://www.ncbi.nlm.nih.gov/pubmed/20648224
http://dx.doi.org/10.2174/1875397301004010034
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