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Updated: Jun 19, 2026

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses
Published on: February 25, 2011
Identification of distinct thiopeptide-antibiotic precursor lead compounds using translation machinery assays
Agata L Starosta1, Haiou Qin, Aleksandra Mikolajka
1Gene Center and Department of Chemistry and Biochemistry, Ludwig-Maximilians University of Munich, Feodor Lynen Strasse 25, 81377 Munich, Germany.
Abstract:
Most thiopeptide antibiotics target the translational machinery: thiostrepton (ThS) and nosiheptide (NoS) target the ribosome and inhibit translation factor function, whereas GE2270A/T binds to the elongation factor EF-Tu and prevents ternary complex formation. We have used several in vitro translational machinery assays to screen a library of thiopeptide antibiotic precursor compounds and identified four families of precursor compounds that are either themselves inhibitory or are able to relieve the inhibitory effects of ThS, NoS, or GE2270T. Some of these precursors represent distinct compounds with respect to their ability to bind to ribosomes. The results not only provide insight into the mechanism of action of thiopeptide compounds but also demonstrate the potential of such assays for identifying lead compounds that might be missed using conventional inhibitory screening protocols.
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