Naslov
Interactions of aminopropyl–azithromycin derivatives, precursors in the synthesis of bioactive macrozones, with E. coli ribosome: NMR and docking studies

Autori
Mikulandra, Ivana ; Jednačak, Tomislav ; Bertoša, Branimir ; Parlov Vuković, Jelena ; Kušec, Iva ; Novak, Predrag

Izvornik
Materials (1996-1944) 14 (2021); 5561, 10

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
azithromycin derivatives ; interactions ; ribosome-bound epitopes ; NMR spectroscopy ; docking

Sažetak
The structure and interactions of several aminopropyl–azithromycin derivatives (1a–c) have been studied by using NMR spectroscopy and docking calculations. Compounds 1a–c are precursors in the synthesis of macrozones, novel bioactive azithromycin–thiosemicarbazone conjugates active against some resistant bacterial strains. Today, bacterial resistance is considered as one of the major threats to human health. Knowledge on drug binding mode and conformations is one of the key factors in the process of designing molecules to fight resistance. In solution state, compounds 1a and 1c exist in the 3-endo-folded-out conformation, while 1b adopts a classical folded- out conformation. 13C and 15N CPMAS NMR spectra pointed towards similar structures in the solid state. The transferred NOESY NMR spectra confirmed binding to the E. coli ribosome and suggest that dominant conformations in the bound state resemble those in the free one. STD experiments identified reactive groups of 1a–c in close contact with the ribosome resembling binding epitopes observed for the related 15 membered macrolides. Docking studies revealed that the studied compounds bind to the same ribosome binding pocket similarly to erythromycin in the crystal state, and that the binding is achieved through H-bonds and van der Waals interactions. The bound conformation is the same as determined by NMR. STD enhancements observed for methylene protons in the aminopropyl side chain indicate additional interactions which contribute to the overall binding energy.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti

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