Abstract
Ferric bleomycin was tested for its ability to catalyze a set of six oxidative reactions characteristic of the heme-containing proteins, cytochrome P-450 and chloroperoxidase. These reactions included peroxyacid decarboxylation and aliphatic hydroxylation as typical cytochrome P-450 chemistries. Peroxyacid-supported oxygen evolution and hydrogen peroxide-mediated chlorination were utilized as characteristic chloroperoxidase reactivities. A typical peroxidative reaction and heteroatom dealkylation, common to both O2 activating enzymes, were also studied. Bleomycin was found to catalyze peroxidation of o-dianisidine. The ferric drug complex was found competent in carrying out N-demethylation of N,N-dimethylaniline when peroxides or peroxyacids or iodosobenzene were used as the oxidants. N-Demethylation was not achieved when N,N-dimethylaniline-N-oxide was substituted as the oxidant under similar conditions. Hydroxylation of cumene and decarboxylation of phenylperacetic acid were not found to be catalyzed by bleomycin. Oxygen evolution from m-chloroperbenzoic acid and chlorination of monochlorodimedone from chloride ion and hydrogen peroxide were found to be catalyzed by bleomycin. Cytochrome P-450cam was also evaluated for O2 evolution, and halogenation activity and was found not to demonstrate such reactivities. The results of this initial survey, along with those of previous studies, appear to indicate that the chemical reactivity of bleomycin can be more closely aligned with the reactivities demonstrated by chloroperoxidase than those of cytochrome P-450.
Highlights
McCarthyand White demonstrated that cytochrome P-450 was unique
When bleomycin was incubated with phenylperacetic acid using a variety of incubation conditions
Ferric bleomycinwas testedfor its ability to catalyze ligation to the metal
Summary
But are found to readily form complexes with a variety of metals [11].Extensive investigations on these metallo-drug (Received for publication, March 11, 1985). Ferric bleomycinwas testedfor its ability to catalyze ligation to the metal [11, 13], iron drug complexes, reminisa set of six oxidative reactions characteristic of the heme-containingproteinsc,ytochrome. The ferric drug complex was found comcent of the cytochromes P-450,are readily formed which can bind dioxygen and carry out site-specific oxidations [5, 14]. Oxygen evolution from m-chloroperbedne-monstrates remarkable correlations with cytochrome P-450 zoicacidandchlorinationofmonochlorodimedone in terms of its physiochemical properties as evaluated by from chloride ion and hydrogen peroxide were found optical absorption [26,27,28,29], ESR[29], Mossbauer [30, 31], tobecatalyzed by bleomycin.Cytochrome P-450,- resonance Raman [32, 33], and magnetic circular dichroism was evaluated forO2evolution, and halogenation spectroscopies [34].
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