STRUCTURE-ACTIVITY STUDIES OF TYLOSIN-RELATED MACROLIDES

The effects of tylosin-related macrolide antibiotics were examined in cell-free protein synthesis (using a coupled transcription-translation system derived from Streptomyces lividans) and against whole cells of that organism. Anti-ribosomal potency was determined primarily by the number and nature of the glycosyl substituents, and was not significa ntly influenced by lactone ring oxidation or sugar methylation. In con trast, uptake of the drugs into S. lividans was influenced, either pos itively or negatively, by each of these structural parameters. The pre sence of erm type I or erm type II resistance genes in S. lividans mar kedly affected the resistance phenotype and studies involving ribosome s from such strains revealed differences in macrolide activity that we re not otherwise apparent.