Solid-phase synthesis of bleomycin A₅ 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 α-D-mannose, α-L-gulose, and α-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.