Molecular biological analysis of sequence-specific DNA recognition and cleavage by metallobleomycins.
The DNase I footprinting analysis shows binding sites of approximately two or three base pairs, in particular 5'-XGC sequences, for the green-colored Co(III) and fully oxidized Fe(III) complexes of bleomycin (BLM). In contrast to covalent attachment of guanine N-7 with aflatoxin B1 or dimethyl sulfate, the modification of guanine 2-amino group with anthramycin remarkably inhibits the DNA cleavages at 5'-GC and 5'-GT sites by the iron and cobalt complex systems of BLM. The present results strongly indicate that metallobleomycin binds in minor groove of B-DNA and that the 2-amino group of guanine adjacent to 5'-side of the cleaved pyrimidine base is one key element of specific 5'-GC or 5'-GT recognition by metallobleomycin. On the basis of these experimental data, possible binding mode of metallobleomycin in B-DNA helix has been proposed by computer-constructed model building.
Kuwahara
J
J
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Sugiura
Y
Y
D001483:Base Sequence; D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000648:ultrastructure*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
D001761:Bleomycin; D004247:DNA