LRET-based HTS of a small-compound library for inhibitors of bacterial RNA polymerase.
Resistance mechanisms against whole classes of antibiotics are currently developing faster than research generates new structurally different biologically active agents. The demand for new antimicrobial drugs has not been matched by the speed of discovery. The interface between sigma and core of bacterial RNA polymerase offers an attractive target for drug discovery, and we have previously described the development of a very robust high-throughput assay for this target based on luminescence resonance energy transfer. Here we describe a semiautomated screen of a commercially available library (Chembridge, San Diego, CA) that led to the identification of four small molecules, two of which have activity in preventing in vitro transcription and growth of Escherichia coli.
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison WI 53706, USA. btglaser@wisc.edu
Bryan T
BT
Glaser
Veit
V
Bergendahl
Nancy E
NE
Thompson
Brian
B
Olson
Richard R
RR
Burgess
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D031541:Fluorescence Resonance Energy Transfer; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D012321:DNA-Directed RNA Polymerases