Dissecting the ribosomal inhibition mechanism of a new ketolide carrying an alkyl-aryl group at C-13 of its lactone ring.
Ketolides are effective not only against macrolide-sensitive bacteria but also against some macrolide-resistant strains. Here we present data regarding a new ketolide with an alkyl-aryl side chain at C-13 of its lactone ring. It behaves as a strong inhibitor of protein synthesis in a model coupled transcription/translation system, although it does not affect the accuracy of translation. In addition, detailed kinetic analysis shows that it slowly forms a very tight, slowly reversible complex with prokaryotic ribosomes, a property that could be correlated with its superior activity compared with erythromycin against Escherichia coli both in vivo and in vitro.
Krokidis
Marios G
MG
Laboratory of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece.
Kostopoulou
Ourania N
ON
Kalpaxis
Dimitrios L
DL
Dinos
George P
GP
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D048628:Ketolides / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000187:drug effects; D012270:Ribosomes / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D048628:Ketolides