The trichodermin group of antibiotics, inhibitors of peptide bond formation by eukaryotic ribosomes

Abstract

We have studied the effects of a number of sesquiterpene antibiotics of the trichodermin group on different steps of the elongation phase in human tonsils and yeast cell-free systems. We have observed that these antibiotics are more active in the human tonsils than in the yeast cell-free systems. When a similar system is considered the antibiotic trichodermin is more active than its derived alcohol trichodermol. Sesquiterpene antibiotics of the trichodermin group do not affect non-enzymatic binding of Ac-Phe-tRNA and either enzymatic or non-enzymatic binding of Phe-tRNA to human tonsil ribosomes. These antibiotics are also without effect on translocation to the P site of Ac-Phe-tRNA bound to the ribosomal A site. All the sesquiterpene antibiotics of the trichodermin group tested (trichodermin, trichodermol, verrucarin A, fusarenon X) are very active inhibitors in the peptide bond formation step. This inhibitory effect of antibiotics of the trichodermin group was observed in the “puromycin reaction” and in the “fragment reaction” assays. Binding of the substrates CACCA-Leu-Ac and UACCA-Leu, respectively, to the donor and the acceptor sites of the peptidyltransferase centre was also studied in this work. We have observed in this system an inhibitory effect in binding of substrates to both the donor and the acceptor site of the peptidyltransferase centre by all the antibiotics of the trichodermin group.