Mode of Action of Antibiotic U-20,661

Antibiotic U-20,661 was shown to inhibit predominantly deoxyribonucleic acid (DNA)-directed ribonucleic acid (RNA) synthesis by binding to the double-stranded DNA template. Specific binding to DNA was verified by difference spectroscopy, reversal of the RNA polymerase inhibitory effect by increasing concentrations of DNA template, and by moderately increasing the melting temperature of double-stranded DNA in the presence of the antibiotic. The RNA polymerase reaction primed with synthetic poly dAT was inhibited considerably, but not completely even with high concentrations of antibiotic. Thus, the agent might bind to adenine or thymidine or both bases in the double-stranded DNA helix.