Tirandamycin: inhibition of ribonucleic Acid polymerase

Tirandamycin acts as a potent inhibitor of ribonucleic acid (RNA) polymerase in bacterial and mammalian cell-free test systems. The antibiotic inhibits the actively synthesizing template-enzyme-nascent RNA complex. Prolonged preincubation of RNA polymerase with tirandamycin prior to assay does not result in a drastic increase of tirandamycin inhibition. Tirandamycin inhibition is not reversed by further addition of deoxyribonucleic acid but is reversed upon further addition of RNA polymerase. Substantial inhibition of RNA polymerase is also obtained when the antibiotic is added at various times after initiation of the reaction. This suggests that tirandamycin interferes with the actively synthesizing template-RNA polymerase complex and inhibits chain elongation rather than chain initiation during RNA synthesis. Tirandamycin also interferes with oxidative phosphorylation in rat liver mitochondria and thus possesses two modes of action.