engleski

Interactions of azithromycin aminopropyl derivatives with E. coli ribosome studied by NMR spectroscopy

Azithromycin is a semisynthetic macrolide antibiotic which possess excellent pharmacokinetic properties and demonstrates satisfactory biological effect. Macrolides are bacteriostatic antibiotics. They exert their biological activity by binding to the 50S subunit of the ribosome. Macrolides are effective against Gram-positive and some Gram-negative bacterial strains [1, 2]. Due to the frequent and improper use of drugs bacterial resistance has emerged, so there is a need to discover more effective antibiotics. Azithromycin aminopropyl derivatives are precursors in synthesis of macrozones. Macrozones are novel bioactive macrolide derivatives and conjugates of azithromycin and thiosemicarbazones [3]. In order to fully understand the mechanism of macrozone bioactivity it is important to determine their bound conformation and interactions with biological targets such as ribosome [4]. In our study, we used NMR spectroscopy to analyse binding of azithromycin derivatives with ribosome isolated from Escherichia coli. Conformations in free and bound state were studied by NOESY (nuclear Overhauser effect spectroscopy) and trNOESY (transferred nuclear Overhauser effect spectroscopy) experiments. STD NMR (Saturation transfer difference Spectroscopy) was used to determine the binding epitopes of azithromycin derivatives. By these techniques relationship between structure and activity will be explored. These results should contribute to the discovery and design of new, more effective macrolide antibiotics.

azithromycin, interactions, macrolides, spectroscopy NMR

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