DNA Cleavage Activity and Metal Complexes of Bleomycin Antibiotics

Abstract

Cleavage of cellular DNA by bleomycin substantially contributes to the antitumor activity of this drug. Two characteristics are necessary for antineoplastic action of bleomycin. First, the bithiazole region of the antibiotic has an affinity for the guanine base of DNA. Second, the β-aminoalanine-pyrimidine-β-hydroxyhistidine portion of the drug is capable of oxygen activation by the complexation. with Fe (II) ion. The role of the gulose-mannose group and unique interaction between the iron-coordination site and the DNA-binding site have been also indicated. Several spectroscopic data have clearly demonstrated that the bleomycin-Fe (II) complex forms a complex with either CO, C2H5NC, or NO. The “site specific oxygen radical” produced from an active bleomycin-Fe (II) complex, would account for the action mechanism of selective DNA base cleavage by bleomycin. In addition, the inactivation mechanism of bleomycin hydrolase and important effect of the fifth axial amino group to iron-coordination on bleomycin activity have been discussed. © 1981, The Society of Synthetic Organic Chemistry, Japan. All rights reserved.