Binding of bleomycin to DNA: intercalation of the bithiazole rings

Abstract

At pH 5.5, binding of bleomycin [an antineoplastic drug] relaxed supercoiled ColEl [Escherichia coli] DNA without breaking it. Binding of tripeptide S (a fragment of the drug containing the bithiazole rings) relaxed and then recoiled supercoiled DNA, at pH 5.5 and at pH 8.0, where bleomycin is normally active. The unwinding angle was 12.degree.. Both compounds lengthened linear DNA by 3.1 .ANG. per molecule bound, and linear dichroism (303-315 nm) of bleomycin bound to linear DNA oriented in an electric field indicated the presence of a chromophore making an angle of 59-61.degree. with the helix axis. Bleomycin binding to DNA probably involves intercalation of the bithiazole rings. In 0.1 M NaCl at pH 8, supercoiled ColEl DNA was broken at a rate 50% greater than relaxed closed circular ColEl DNA. Since supercoiling increases the affinity of DNA for intercalators, intercalative binding probably is involved in bleomycin-induced breakage of DNA.