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 characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against 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 correlation methods. The study of ketolide-ribosome interaction has been investigated using 2D transferred nuclear Overhauser effect spectroscopy (TRNOESY). A comparison of the conformations in solution and bound to ribosomes was made with those of previous macrolides. This study can highlight some of the significant differences between RU 004 and other antibiotics.