Binding of Bleomycin to DNA: Intercalation of the Bithiazole Rings

Abstract

At pH 5.5, binding of bleomycin relaxed supercoiled ColEl DNA without breaking it. Binding of tripeptide S, a fragment of the drug containing the bithiazole rings, also 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°. Both compounds lengthened linear DNA by 3.1 Åper molecule bound, and linear dichroism (303-315 nm) of bleomycin hound to linear DNA oriented in an electric field indicated the presence of a chromophore making an angle of 59-61° with the helix axis. These results strongly suggest that bleomycin binding to DNA 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, this result suggests that intercalative binding is involved in bleomycin-induced breakage of DNA. © 1979, American Chemical Society. All rights reserved.