[Mechanism of action of bleomycin at the molecular level]

On the basis of the structures of bleomycin (BLM) and its copper-complex, which were determined by us in 1978, it has become possible to discuss the mechanism of antitumor action of BLM of the molecular level. BLM is a bifunctional compound comprised of a binding site to DNA and a reaction site with DNA. The positive charge at the terminal amine interacts with negatively charged DNA by electrostatic attraction and the planar bithiazole moiety intercalates with DNA. The activated molecular oxygen at the axial site of the BLM-Fe (II) complex reacts with DNA. The mechanism of the activation of oxygen coupled with the Fe(II)-Fe(III) redox cycle is discussed. The degradation process of DNA by BLM and the bases-specific cleavage of DNA are described. Finally, the behavior of BLM in animals is described.