Solid-phase synthesis of bleomycin A(5) and three monosaccharide analogues: exploring the role of the carbohydrate moiety in RNA cleavage.
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.
Thomas
Craig J
CJ
Department of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA.
Chizhov
Alexander O
AO
Leitheiser
Christopher J
CJ
Rishel
Michael J
MJ
Konishi
Kazuhide
K
Tao
Zhi-Fu
ZF
Hecht
Sidney M
SM
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
D009005:Monosaccharides; D001761:Bleomycin; C025703:bleomycetin; D012313:RNA; D004247:DNA