Naslov
A Systematic Approach to Understanding Ribosome-Macrolide Interactions: NMR and Modeling Studies of Oleandomycin and Its Derivatives

Autori
Novak, Predrag ; Tatić, Iva ; Tepeš, Predrag ; Koštrun, Sanja ; Barber, Jill

Izvornik
JOURNAL OF PHYSICAL CHEMISTRY A (1089-5639) 110 (2006), 1; 580-588

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

Ključne riječi
oleandomycin; NMR; derivatives

Sažetak
The three-dimensional structures of oleandomycin (1) and its derivatives oleandomycin-9-oxime (2) and 10, 11- anhydrooleandomycin (3) were determined in different solvents by the combined use of NMR and molecular modeling methods. The experimental NMR data were compared with the results of molecular modeling and known crystal structures of the related molecules. It was shown that the dominant conformation of the lactone ring is the folded-out conformation with some amounts of the folded-in one depending on the solvent and temperature, while desosamine and cladinose sugars adopt the usual chair conformations. Modeling calculations provided evidence for conformational changes in the upper lactone region as well. Saturation transfer difference (STD) NMR experiments have provided information on the binding epitopes of 1-3 in complexes with E. coli ribosomes. The obtained molecular surfaces in close contact with ribosomes were compared with recently available 3D structures of the related macrolide-ribosome complexes, and the observed differences were discussed. The knowledge gained from this study can serve as a platform for the design of novel macrolides with an improved

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA