engleski

How can NMR spectroscopy reveal binding epitopes of macrolide antibiotics?

Macrolide antibiotics are effective therapeutic agents for treating infectious diseases owing to their high efficacy and safety [1, 2]. Macrolides bind to the bacterial ribosomal 23S rRNA at the peptidyl transferase region and block the exit of the nascent peptide. In spite of a number of existing macrolide antibiotics, the emerging multi‐drug resistant microbial pathogens present serious and challenging issues in medical treatment which demands novel and more effective 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 drug design. We have shown that an approach which combines one‐ and two‐dimensional NMR methods and molecular modelling calculations could successfully be applied to conformational analysis of free and bound macrolides [3]. 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 [4]. The application of NMR diffusion and solvent paramagnetic relaxation experiments can further reveal interaction strength and localization of macrolide antibiotics bound to their targets [4, 5]. In this talk the binding epitopes of macrolide interactions with ribosomes, membrane mimetics and bile acids will be discussed. The knowledge gained from these studies can serve as a platform for the design of novel compounds with an improved biological profile

macrolide antibiotics ; epitopes ; NMR

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