Bleomycin-構造と機能--プロリン水酸化酵素とDNA鎖切断に対するBleomycinの効果

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The activity of purified prolyl hydroxylase was enhanced about 3-fold by addition of bleomycin in the assay mixture. Various members of the bleomycin family, their derivatives and degradation products were investigated for activities against prolyl hydroxylase together with their activities of DNA chain breakage to determine relationships between the structure of bleomycin and its various actions. All the bleomycins with various terminal amine parts and desamide bleomycin stimulated the enzymatic activity but, did not exhibit an effect on DNA chain breakage. The stimulatory activity of bleomycin was not decreased by hydrolysis with 0.3 N H<SUB>2</SUB>SO<SUB>4</SUB> at 80°C for 6 hours, conditions which liberates the sugar moiety, but was eliminated by hydrolysis with 6 N HCl at 105°C for 24 hours. On the other hand, both treatments decreased the DNA chain breakage activity of bleomycin. Column chromatographic studies showed that bleomycin formed a complex with ferrous ion, one of the cofactors of prolyl hydroxylase. Optical spectral studies revealed that all the bleomycins and their hydrolysates which stimulated the prolyl hydroxylase activity made complexes with ferrous ion. From these results it seems that bleomycin may interact with ferrous ion and that bleomycin-ferrous ion may affect the rate of peptidyl proline hydroxylation and DNA chain breakage.
学校法人昭和大学・昭和医学会の論文