Naslov
Exploring macrolide binding modes by NMR spectroscopy

Autori
Novak, Predrag

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
CEUM 2022, Warsaw / - , 2022, 10-10

Skup
Central European NMR Symposium

Mjesto i datum
Varšava, Poljska, 21.09.2022. - 23.09.2022

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
macrolides, macrozones, interactions, binding modes, NMR spectroscopy

Sažetak
15- membered macrolides are well-known class of antibacterials widely prescribed to treat upper and lower respiratory tract infections 1. Azithromycin is a semi-synthetic macrolide antibiotic derived from erythromycin possessing broad spectrum of antibacterial potency and favorable pharmacokinetics. Similar to other macrolide antibiotics it exerts its activity by binding to the bacterial ribosomal 23S rRNA in domain V at the peptidyl transferase region and blocks the exit tunnel which in turn inhibits the bacterial protein synthesis. However, bacterial resistance to marketed antibiotics is growing rapidly and represents one of the major hazards to human health worldwide. Recently discovered conjugates of azithromycin and thiosemicarbazones, the macrozones, represent new class of macrolide derivatives that exhibit promising activities against resistant pathogens 2-3. Interaction studies of macrolide antibiotics and some selected macrozones with their biological targets will be presented in this talk. NMR experiments such as transferred nuclear Overhauser effect spectroscopy (trNOESY), saturation transfer difference (STD), diffusion and solvent paramagnetic relaxation experiments (PRE) in combination with molecular modelling have been employed to characterize binding modes and epitopes and asses bound conformations [4-6]. These data can serve as a platform for design of novel inhibitors with an improved biological profile.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA