BLEOMYCIN-MEDIATED DEGRADATION OF ARISTEROMYCIN-CONTAINING DNA - NOVEL DEHYDROGENATION ACTIVITY OF IRON(II) BLEOMYCIN

The antitumor antibiotic bleomycin (BLM) induces C-H bond scission at the C4' of deoxyribose moiety of DNA in the presence of Fe(II) and O2. To investigate the primary oxidation step, 2'-deoxyaristeromycin (Ar) possessing a cyclopentane ring instead of a ribofuranose ring was incorporated into the BLM-cleaving site of synthetic oligonucleotide d (GGArAGG). It was found that an unprecedented dehydrogenation occurs effectively at the C4' and C6' positions of the Ar moiety to give 2'-deoxyneplanocin A containing oligonucleotide together with a minor but stereospecific C4' hydroxylation in the Fe(II)-BLM-mediated degradation of duplex d(GGArAGG)-d(CCTTCC). An intermediate C4' carbocation derived from one-electron oxidation of initially formed C4' radical has been proposed for the dehydrogenation reaction.