Current Chemical Genomics and Translational Medicine
2010, 4 : 34-42Published online 2010 May 26. DOI: 10.2174/1875397301004010034
Publisher ID: CCGTM-4-34
RESEARCH ARTICLE
Novel Inhibitors of RecA ATPase Activity
1
Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, 27707, USA
2 UNC Eshelman School of Pharmacy, Division of Medicinal Chemistry and Natural Products, The University of North Carolina at Chapel Hill, CB #7568, Chapel Hill, North Carolina, 27599-7568, USA
* Address correspondence to this author at the 1801 Fayetteville St, BRITE Rm 2015, North Carolina Central University, Durham, North Carolina 27707, USA; Tel: 919-530-6251; Fax: 919-530-6600; E-mail: jsexton@nccu.edu
2 UNC Eshelman School of Pharmacy, Division of Medicinal Chemistry and Natural Products, The University of North Carolina at Chapel Hill, CB #7568, Chapel Hill, North Carolina, 27599-7568, USA
* Address correspondence to this author at the 1801 Fayetteville St, BRITE Rm 2015, North Carolina Central University, Durham, North Carolina 27707, USA; Tel: 919-530-6251; Fax: 919-530-6600; E-mail: jsexton@nccu.edu
ABSTRACT
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.