A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP.

J Med Chem

School of Pharmacy, Division of Medicinal Chemistry and Natural Products, University of North Carolina at Chapel Hill, CB 7360, Chapel Hill, North Carolina 27599-7360, USA.

Published: August 2005

We report that N(6)-(1-naphthyl)-ADP inhibits the Escherichia coli RecA protein in vitro. A novel rapid screen identified it as a potent inhibitor of RecA nucleoprotein filament formation, and further characterization established it as an ATP-competitive inhibitor of RecA-catalyzed ATP hydrolysis. This and other inhibitors of RecA activities represent a new approach for understanding the molecular targets and pathways involved in the evolution of antibiotic resistance in bacteria.

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http://dx.doi.org/10.1021/jm050113zDOI Listing

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