Conformation of macrolides antibiotics bound to ribosomes as determined from transferred nuclear Overhauser effect spectroscopy

The ribosomal bound conformation of 14-membered-ring macrolides roxithromycin, erythromycin A and their methylated derivatives has been elucidated from study of the macrolide-ribosome interactions using transferred nuclear Overhauser effect (TRNOE). Only one specific conformation is preferred in the bound state. The bioactive macrolide antibiotics studied displayed a strong NMR response, while their inactive major metabolites displayed blank TRNOESY spectrum. TRNOE analysis established correlation between the bound state conformation of these active compounds and the major conformation (A1a) in solution.