title: Structure-activity studies of tylosin-related macrolides.
abstract: 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 significantly influenced by lactone ring oxidation or sugar methylation. In contrast, uptake of the drugs into S. lividans was influenced, either positively or negatively, by each of these structural parameters. The presence of erm type I or erm type II resistance genes in S. lividans markedly affected the resistance phenotype and studies involving ribosomes from such strains revealed differences in macrolide activity that were not otherwise apparent.
authors.affiliation: Department of Biochemistry, University of Leicester, U.K.
authors.forename: S A
authors.initials: SA
authors.lastname: Fish
authors.forename: E
authors.initials: E
authors.lastname: Cundliffe
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002474:Cell-Free System; D010084:Oxidation-Reduction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012270:Ribosomes / Q000378:metabolism; D013302:Streptomyces / Q000378:metabolism; D013329:Structure-Activity Relationship; D015645:Tylosin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D015645:Tylosin