engleski

NMR approaches to disentangling interactions of macrolide antibiotics,

Macrolide antibiotics are effective therapeutic agents for treating infectious diseases owing to their high efficacy and safety. They inhibit bacterial protein biosynthesis by binding to the ribosomal 23S rRNA at the peptidyl transferase region and block the exit tunnel through which the nascent peptides leave the ribosome. In spite of a number of existing antibiotics, the emerging multi-drug resistant microbial pathogens present serious and challenging problems which demand novel and more potent antimicrobial agents to be discovered. An effective approach to overcoming this problem is to understand the principles of how these drugs interact with the ribosome. NMR spectroscopy is one of the most powerful and valuable methods in conformational analysis and structure-based inhibitor design. We have shown that an approach which combines one- and two-dimensional NMR methods and molecular modelling calculations could sucessfully be applied to conformational analysis of free and bound macrolides [1]. Furthermore, NOE based NMR techniques such as transferred NOE (tr-NOE) and saturation transfer difference (STD) provide further information on the bound state conformation and binding epitopes [2]. The application of NMR self-diffusion and solvent paramagnetic relaxation experiments can reveal the interaction strength and localization of macrolide antibiotics bound to their targets [3]. In this talk the interactions of macrolides with ribosomes, membrane mimetics and bile acids will be presented and discussed [4]. The knowledge gained from these studies can serve as a platform for the design of novel compounds with an improved biological profile.

Macrolide antibiotics ; interactions ; NMR spectroscopy

nije evidentirano