Solid-Phase Synthesis of Bleomycin A sub(5) and Three Monosaccharide Analogues: Exploring the Role of the Carbohydrate Moiety in RNA Cleavage

The solid-phase synthesis of bleomycin A sub(5) (BLM A sub(5)) 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 A sub(5). 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 A sub(5) and each of the carbohydrate analogues constitutes an important advance in the continuing mechanistic studies of bleomycin.