Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1977 Sep 15;166(3):399–409. doi: 10.1042/bj1660399

Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes

Christopher J Carter 1, Michael Cannon 1
PMCID: PMC1165022  PMID: 597234

Abstract

1. The inhibitory actions of ten trichothecene antibiotics were investigated, in reticulocyte cell-free systems synthesizing protein in vitro, by studying polyribosome profiles and kinetics of amino acid incorporation in the presence or absence of the drugs. 2. The modes of action observed were critically dependent on the drug concentrations used, but the antibiotics tested could be divided into four distinct groups, each exerting a characteristic inhibitory response. 3. The inhibitory action observed in every case was controlled by the chemical structure of the individual trichothecene and in particular was closely related to the nature of the substituent groups present on C-3, C-4, C-8 and C-15 of the molecule.

Full text

PDF
399

Selected References

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

  1. Barbacid M., Vazquez D. Binding of (acetyl-14C)trichodermin to the peptidyl transferase centre of eukaryotic ribosomes. Eur J Biochem. 1974 May 15;44(2):437–444. doi: 10.1111/j.1432-1033.1974.tb03501.x. [DOI] [PubMed] [Google Scholar]
  2. Cannon M., Jimenez A., Vazquez D. Competition between trichodermin and several other sesquiterpene antibiotics for binding to their receptor site(s) on eukaryotic ribosomes. Biochem J. 1976 Nov 15;160(2):137–145. doi: 10.1042/bj1600137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cannon M., Smith K. E., Carter C. J. Prevention, by ribosome-bound nascent polyphenylalanine chains, of the functional interaction of t-2 toxin with its receptor site. Biochem J. 1976 May 15;156(2):289–294. doi: 10.1042/bj1560289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carrasco L., Barbacid M., Vazquez D. The trichodermin group of antibiotics, inhibitors of peptide bond formation by eukaryotic ribosomes. Biochim Biophys Acta. 1973 Jun 23;312(2):368–376. doi: 10.1016/0005-2787(73)90381-x. [DOI] [PubMed] [Google Scholar]
  5. Carter C. J., Cannon M., Smith K. E. Inhibition of protein synthesis in reticulocyte lysates by trichodermin. Biochem J. 1976 Jan 15;154(1):171–178. doi: 10.1042/bj1540171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cundliffe E., Cannon M., Davies J. Mechanism of inhibition of eukaryotic protein synthesis by trichothecene fungal toxins. Proc Natl Acad Sci U S A. 1974 Jan;71(1):30–34. doi: 10.1073/pnas.71.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cundliffe E., Davies J. E. Inhibition of initiation, elongation, and termination of eukaryotic protein synthesis by trichothecene fungal toxins. Antimicrob Agents Chemother. 1977 Mar;11(3):491–499. doi: 10.1128/aac.11.3.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gardner D., Glen A. T., Turner W. B. Calonectrin and 15-deacetylcalonectrin, new trichothecanes from Calonectria nivalis. J Chem Soc Perkin 1. 1972;20:2576–2578. doi: 10.1039/p19720002576. [DOI] [PubMed] [Google Scholar]
  9. Macdonald J. S., Goldberg I. H. An effect of pactamycin on the initiation of protein synthesis in reticulocytes. Biochem Biophys Res Commun. 1970 Oct 9;41(1):1–8. doi: 10.1016/0006-291x(70)90460-2. [DOI] [PubMed] [Google Scholar]
  10. Schindler D., Grant P., Davies J. Trichodermin resistance--mutation affecting eukaryotic ribosomes. Nature. 1974 Apr 5;248(448):535–536. doi: 10.1038/248535a0. [DOI] [PubMed] [Google Scholar]
  11. Schindler D. Two classes of inhibitors of peptidyl transferase activity in eukaryotes. Nature. 1974 May 3;249(452):38–41. doi: 10.1038/249038a0. [DOI] [PubMed] [Google Scholar]
  12. Smith K. E., Cannon M., Cundliffe E. Inhibition at the initiation level of eukaryotic protein synthesis by T-2 toxin. FEBS Lett. 1975 Jan 15;50(1):8–12. doi: 10.1016/0014-5793(75)81028-3. [DOI] [PubMed] [Google Scholar]
  13. Tate W. P., Caskey C. T. Peptidyltransferase inhibition by trichodermin. J Biol Chem. 1973 Nov 25;248(22):7970–7972. [PubMed] [Google Scholar]
  14. Ueno Y., Nakajima M., Sakai K., Ishii K., Sato N. Comparative toxicology of trichothec mycotoxins: inhibition of protein synthesis in animal cells. J Biochem. 1973 Aug;74(2):285–296. [PubMed] [Google Scholar]
  15. Wei C. M., Campbell I. M., McLaughlin C. S., Vaughan M. H. Letter: Binding of trichodermin to mammalian ribosomes and its inhibition by other 12,13-epoxytrichothecenes. Mol Cell Biochem. 1974 May 30;3(3):215–219. doi: 10.1007/BF01686646. [DOI] [PubMed] [Google Scholar]
  16. Wei C. M., Hansen B. S., Vaughan M. H., Jr, McLaughlin C. S. Mechanism of action of the mycotoxin trichodermin, a 12,13-epoxytrichothecene. Proc Natl Acad Sci U S A. 1974 Mar;71(3):713–717. doi: 10.1073/pnas.71.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wei C. M., McLaughlin C. S. Structure-function relationship in the 12,13-epoxytrichothecenes. Novel inhibitors of protein synthesis. Biochem Biophys Res Commun. 1974 Apr 8;57(3):838–844. doi: 10.1016/0006-291x(74)90622-6. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES