Naslov
Epitope mapping of macrolide antibiotics in interactions with ribosomes

Autori
Novak, Predrag

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

Izvornik
CEUM 2008 : book of abstracts / Smrečki, Vilko - Zagreb : Institut Ruđer Bošković, 2008

ISBN
978-953-6690-77-0

Skup
Central European NMR Symposium (10 ; 2008)

Mjesto i datum
Zagreb, Hrvatska, 29.09.2008. - 30.09.2008

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
macrolide antibiotisc; NMR; ribosom; interactions

Sažetak
Macrolide antibiotics are therapeutically important molecules that are effective inhibitors of bacterial protein biosynthesis. The increasing resistance to ribosome-targeting antibiotics has become a global problem and much effort is now directed toward new and more potent classes of drugs to overcome resistance mechanisms. An effective approach to overcoming this problem is to understand the principles of how these drugs interact with the ribosome. Recently available crystal structures of some ribosome-macrolide complexes have thrown new light on the binding mechanisms and hence provide a good basis for the design of new ligands and inhibitors. However, when analysing solid state structures of ribosome-macrolide complexes one should keep in mind the discrepancies between structures obtained for halophilic archeon H. marismortui and D. radiodurans. The proposed models differ significantly even though ribosomal 50S subunits of the two bacteria have drug binding sites whose sequences are highly conserved. Therefore, important steps in the process of drug design should also include elucidation of the solution-state structures of free and bound ligand molecules since the structural features of the complex may not be exactly the same in solution and in the solid state. One and two-dimensional NMR techniques have proven usefull in conformational analysis and structure-based inhibotor design. Here, an approach which combine NMR parameterts such as spin-spin coupling constants, nOe and relaxation times coupled with molecular modelling is employed to study free conformations of macrolides. Furthermore, an application of transferred nOe and STD experiments provides information on the bound state conformation and binding epitopes. The knowledge gained from these studies can serve as a platform for the design of novel compounds with an improved biological profile.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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