Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Jul;70(7):2072–2076. doi: 10.1073/pnas.70.7.2072

Action of Rifamycin Derivatives on RNA Polymerase of Human Leukemic Lymphocytes

Ming-Jer Tsai 1,2,3, Grady F Saunders 1,2,3
PMCID: PMC433668  PMID: 4516206

Abstract

The mechanism of inhibition of human RNA polymerase by four rifamycin derivatives was investigated. Derivative AF/013 (3-formyl rifamycin SV:O-n-octyloxime) with strong hydrophobic side chains prevents the polymerase from binding to DNA and also affects the size of RNA synthesized. Derivative PR/19 (3′-acetyl-1′-benzyl-2′-methylpyrrolo[3,2-c]-4-desoxy-rifamycin SV) only affects RNA synthesis when RNA polymerase has been previously incubated with the drug or when the reaction was performed at high salt concentration [0.14 M (NH4)2-SO4]. Our results suggest that these drugs exert their inhibitory actions by binding to the enzyme instead of DNA.

Keywords: (AF/013)(PR/19)

Full text

PDF
2076

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burgess R. R. RNA polymerase. Annu Rev Biochem. 1971;40:711–740. doi: 10.1146/annurev.bi.40.070171.003431. [DOI] [PubMed] [Google Scholar]
  2. Butterworth P. H., Cox R. F., Chesterton C. J. Transcription of mammalian chromatin by mammalian DNA-dependent RNA polymerases. Eur J Biochem. 1971 Nov 11;23(2):229–241. doi: 10.1111/j.1432-1033.1971.tb01613.x. [DOI] [PubMed] [Google Scholar]
  3. Chamberlin M. J., Ring J. Characterization of T7 specific RNA polymerase. 3. Inhibition by derivatives of rifamycin SV. Biochem Biophys Res Commun. 1972 Nov 15;49(4):1129–1136. doi: 10.1016/0006-291x(72)90330-0. [DOI] [PubMed] [Google Scholar]
  4. Chambon P., Ramuz M., Mandel P., Doly J. Inhibition of RNA polymerase by sodium polyethylene sulphonate. Biochim Biophys Acta. 1967 Dec 19;149(2):584–586. doi: 10.1016/0005-2787(67)90186-4. [DOI] [PubMed] [Google Scholar]
  5. Jones O. W., Berg P. Studies on the binding of RNA polymerase to polynucleotides. J Mol Biol. 1966 Dec 28;22(2):199–209. doi: 10.1016/0022-2836(66)90126-4. [DOI] [PubMed] [Google Scholar]
  6. Lindell T. J., Weinberg F., Morris P. W., Roeder R. G., Rutter W. J. Specific inhibition of nuclear RNA polymerase II by alpha-amanitin. Science. 1970 Oct 23;170(3956):447–449. doi: 10.1126/science.170.3956.447. [DOI] [PubMed] [Google Scholar]
  7. Meilhac M., Tysper Z., Chambon P. Animal DNA-dependent RNA polymerases. 4. Studies on inhibition by rifamycin derivatives. Eur J Biochem. 1972 Jul 13;28(2):291–300. doi: 10.1111/j.1432-1033.1972.tb01913.x. [DOI] [PubMed] [Google Scholar]
  8. Roeder R. G., Rutter W. J. Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms. Nature. 1969 Oct 18;224(5216):234–237. doi: 10.1038/224234a0. [DOI] [PubMed] [Google Scholar]
  9. Sippel A., Hartmann G. Mode of action of rafamycin on the RNA polymerase reaction. Biochim Biophys Acta. 1968 Mar 18;157(1):218–219. doi: 10.1016/0005-2787(68)90286-4. [DOI] [PubMed] [Google Scholar]
  10. Umezawa H., Mizuno S., Yamazaki H., Nitta K. Inhibition of DNA-dependent RNA synthesis by rifamycins. J Antibiot (Tokyo) 1968 Mar;21(3):234–236. doi: 10.7164/antibiotics.21.234. [DOI] [PubMed] [Google Scholar]
  11. Ward D. C., Reich E., Goldberg I. H. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(3689):1259–1263. doi: 10.1126/science.149.3689.1259. [DOI] [PubMed] [Google Scholar]
  12. Weaver R. F., Blatti S. P., Rutter W. J. Molecular structures of DNA-dependent RNA polymerases (II) from calf thymus and rat liver. Proc Natl Acad Sci U S A. 1971 Dec;68(12):2994–2999. doi: 10.1073/pnas.68.12.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wehrli W., Staehelin M. Actions of the rifamycins. Bacteriol Rev. 1971 Sep;35(3):290–309. doi: 10.1128/br.35.3.290-309.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES