CONFORMATIONAL-ANALYSIS OF KETOLIDE, CONFORMATIONS OF RU-004 IN SOLUTION AND BOUND TO BACTERIAL-RIBOSOMES

A new structurally distinct class of 14--membered-ring macrolides is c haracterized by a keto-function instead of the cladinose sugar, well-k nown for its fragility even in weakly acidic media. This new class cal led ketolides is endowed with remarkable antibacterial activity agains t macrolide-resistant strains. A complete assignment of the H-1 and C- 13 NMR spectra of RU 004 in deuteriochloroform, methanol-d(4) and D2O has been made using different two-dimensional (2D) chemical-shift corr elation methods. The study of ketolide-ribosome interaction has been i nvestigated using 2D transferred nuclear Overhauser effect spectroscop y (TRNOESY). A comparison of the conformations in solution and bound t o ribosomes was made with those of previous macrolides. This study can highlight some of the significant differences between RU 004 and othe r antibiotics.