Abstract
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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- FOX C. F., ROBINSON W. S., HASELKORN R., WEISS S. B. ENZYMATIC SYNTHESIS OF RIBONUCLEIC ACID. III. THE RIBONUCLEIC ACID-PRIMED SYNTHESIS OF RIBONUCLEIC ACID WITH MICROCOCCUS LYSODEIKTICUS RIBONUCLEIC ACID POLYMERASE. J Biol Chem. 1964 Jan;239:186–195. [PubMed] [Google Scholar]
- Reusser F., Bhuyan B. K. Comparative studies with three antibiotics binding to deoxyribonucleic acid. J Bacteriol. 1967 Sep;94(3):576–579. doi: 10.1128/jb.94.3.576-579.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reusser F. Mode of action of antibiotic U-20,661. J Bacteriol. 1967 Jan;93(1):65–70. doi: 10.1128/jb.93.1.65-70.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reusser F. Tirandamycin: inhibition of oxidative phosphorylation in rat liver mitochondria. Infect Immun. 1970 Jul;2(1):82–88. doi: 10.1128/iai.2.1.82-88.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wehrli W., Knüsel F., Schmid K., Staehelin M. Interaction of rifamycin with bacterial RNA polymerase. Proc Natl Acad Sci U S A. 1968 Oct;61(2):667–673. doi: 10.1073/pnas.61.2.667. [DOI] [PMC free article] [PubMed] [Google Scholar]