Antibacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site

Abstract

A new twist of RNA fate: Site-selective chemical functionalization at the C2"-OH group of paromomycin (1) afforded a novel analogue with potent inhibitory activity against several bacterial strains, including a multidrug-resistant S. aureus (MRSA) strain. X-ray cocrystal-structure determination of the complex with the A site of E. coli RNA revealed a new mode of binding in which significant conformational and positional changes had taken place in rings III and IV.