Self-inactivation of Fe(II)-bleomycin

Abstract

Fe(II)-Bleomycin is activated in air to form an electron paramagnetic resonance (EPR)-active species, termed "activated bleomycin", that cleaves DNA, when present. When DNA is absent, the potential DNA cleavage activity is lost and the drug becomes self inactivated. A method is described for the preparation and purification of this self-inactivated product from bleomycin A2, together with some of its physical properties. It is shown that the loss of DNA cleavage activity parallels an alteration of bithiazole fluorescence, attributed to chemical change at this residue. EPR evidence is brought forth that the Cu(II) binding site of inactivated bleomycin in not altered, nor is the ability to form a species with Fe(II) and O2 having the identical spectroscopic signature as activated bleomycin.