DNA Strand Scission by Bleomycin Group Antibiotics

Abstract

Certain properties of the bleomycin analogs deglycobleomycin A2 and decarbamoylbleomycin A2 have been characterized. In common with bleomycin A2, both deglycobleomycin A2 and decarbamoylbleomycin A2 were found to mediate DNA degradation in the presence of Fe(II)+O2. Both analogs were found to have essentially the same sequence selectivity for DNA strand scission as bleomycin A2 when a 5''-[23P]-end-labeled linear duplex DNA derived from SV40 DNA was employed as a substrate. Product analysis for the three analogs was carried out by assay for malondialdehyde (precursors) after digestion of calf thymus DNA, and also by hplc analysis of the digestion products formed from the dodecanucleotide d(CGCTTTAAAGCG). All three Fe(II) .cntdot. bleomycin A2 analogs produced the same products, albeit not in the same relative amounts.