title: Solid-phase synthesis of bleomycin A(5) and three monosaccharide analogues: exploring the role of the carbohydrate moiety in RNA cleavage.
abstract: The solid-phase synthesis of bleomycin A5 (BLM A5) and three monosaccharide analogues is presented. The monosaccharide analogues incorporated alpha-d-mannose, alpha-l-gulose, and alpha-l-rhamnose moieties in lieu of the disaccharide normally present in BLM A5. Also explored were the abilities of each of the monosaccharide congeners to cleave a 53-nt RNA. The elaboration of these carbohydrate-modified bleomycin analogues helps to define the role of the disaccharide moiety during the RNA cleavage event. The relatively facile solid-phase synthesis of bleomycin A5 and each of the carbohydrate analogues constitutes an important advance in the continuing mechanistic studies of bleomycin.
authors.affiliation: Department of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Chizhov
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Leitheiser
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rishel
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Konishi
authors.forename: Zhi-Fu
authors.initials: ZF
authors.lastname: Tao
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D001483:Base Sequence; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000737:chemistry* / Q000494:pharmacology*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009005:Monosaccharides; D001761:Bleomycin; C025703:bleomycetin; D012313:RNA; D004247:DNA