Abstract
A range of antibiotics and other drugs was tested for possible inhibitory activity toward the DNA-dependent RNA polymerase of Escherichia coli. Several agents believed to interfere primarily with protein or DNA synthesis in microorganisms were shown to have no significant effect on AMP incorporation into RNA by the enzyme system. Neomycin, Antrycide, and pentamidine precipitated the DNA primer and gave substantial inhibition; suramin, prothidium bromide, proflavin, and ethidium bromide were more powerfully inhibitory, and actinomycin D was the most potent inhibitor found. These results are discussed with reference to the probable modes of action of the drugs in vivo.
Inhibition by ethidium bromide was found to be related to the concentration of DNA, as would be expected if the inhibition were due to the drug’s forming a complex with the primer. Calculations of the expected level of binding of ethidium to DNA under the assay conditions led to the conclusion that RNA polymerase activity was inhibited in direct proportion to the amount of drug bound to the primer.
ACKNOWLEDGMENTS This work was supported by a Scholarship for training in research methods from the Medical Research Council. The author wishes to thank Dr. Kenneth McQuillen for much valuable discussion and the staff of the Carnegie Institution of Washington, Department of Terrestrial Magnetism, for assistance in the preparation of the manuscript.
- Copyright ©, 1965, by Academic Press Inc.
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