title: Importance of the 6'-hydroxy group and its configuration for apramycin activity.
abstract: A series of apramycin derivatives was prepared and investigated for antibacterial activity and the ability to inhibit protein synthesis in cell-free translation assays. The effect of various modifications at the 6'- and N7'-positions on antiribosomal activity is discussed in terms of their influence on drug binding to specific residues in the decoding A-site. These studies contribute to the development of a structure-activity relationship for the antibacterial activity of the apramycin class of aminoglycosides and to the future design and development of more active and less toxic antibiotics.
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202 (USA).
authors.forename: Appi Reddy
authors.initials: AR
authors.lastname: Mandhapati
authors.forename: Dimitri
authors.initials: D
authors.lastname: Shcherbakov
authors.forename: Stefan
authors.initials: S
authors.lastname: Duscha
authors.forename: Andrea
authors.initials: A
authors.lastname: Vasella
authors.forename: Erik C
authors.initials: EC
authors.lastname: Böttger
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002240:Carbohydrate Sequence; D020134:Catalytic Domain / Q000187:drug effects; D002474:Cell-Free System; D008969:Molecular Sequence Data; D009328:Nebramycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D012270:Ribosomes / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D009328:Nebramycin; C011666:apramycin
keywords: RNA; aminoglycoside antibiotics; antibacterial activity; ototoxicity; ribosomes