jp0526243_si_001.pdb (8.78 kB)
Systematic Approach to Understanding Macrolide−Ribosome Interactions: NMR and Modeling Studies of Oleandomycin and Its Derivatives†
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posted on 2006-01-19, 00:00 authored by Predrag Novak, Iva Tatić, Predrag Tepeš, Sanja Koštrun, Jill BarberThe 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 biological profile.