Bleomycin interactions with DNA studies on the role of the C-terminal cationic group of bleomycin A2 in association with and degradation of DNA

Abstract

The role of the cationic dimethylsulfonium group of Abeomycin A2 in the binding of the drug to poly(dA-dT) has been investigated b proton NMR studies on the S-demethyated derivative. In contrast to the parent drug, the demethyl congener shows no intercalation of the aromatic bithiazole group which is adjacent to the former cationic group. However, chemical studies show that the demethyl derivative retains the capability to degrade DNA in the presence of iron(II), albeit at a reduced rate and to a lesser extent than the intact bleomycin A2. Thus, the cationic group is necessary for the intercalation of the bithiazole portion of the drug molecule; however, intercalation is not essential for the degradation of DNA.