The DNA-cleaving activity of bleomycin,1an antitumor glycopeptide antibiotic, had been shown in vitro to depend on the formation of activated bleomycin, a drug complex containing Fe(III) and oxygen.2,3 This complex can be formed with Fe(III) and peroxide, Fe(III) plus reductants and O2, or Fe(II) and O2. Other metals gave no detectable DNA degradation in O2-dependent reactions, and many inhibit the iron-requiring reaction.4 We now report DNA degradation by Mn(II)-bleomycin in the presence of H2O2. This activity is not due to endogenous iron salts and differs from that of iron-bleomycin in several respects. DNA does not inhibit the Mn(II)-bleomycin reaction, as it does the iron-bleomycin reaction, but optimal activity is only 1−3% of that of the Fe(III)-drug complex with H2O2. DNA products include free bases and base propenals, 5 as with iron bleomycin, but in different proportions. Aerobic solutions of reducing agents such as 2-mercaptoethanol cannot substitute for peroxide in the Reaction with Mn(II) as they do in the reaction with Fe-(III). In this respect, Mn(II)-bleomycin parallels the behavior of Mn(II)-cytochrome P-450, which cannot be activated reductively but can be activated with peroxides.6.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Inorganic Chemistry