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 02. 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 Fe11- 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.
ASJC Scopus subject areas
- Colloid and Surface Chemistry