Sequence-specific recognition and cleavage of DNA by metallobleomycin: minor groove binding and possible interaction mode.

Abstract

The DNase I cleavage-inhibition analysis shows binding sites of approximately 2 or 3 base pairs-in particular, 5' N-G-C sequences-for the green-colored Co"' and fully oxidized Fe"' complexes of bleomycin. The apparent binding constant of the bleomycin-Co"' complex is quite similar for glucosylated and nonglucosylated phage T4 DNAs,

Sequence-specific Changes in the Metal Site of Ferric Bleomycin Induced by the Binding of DNA

“…Since the drug binds to both of the oligomers, as demonstrated by optical spectroscopy, this result shows that the bithiazole binds d(CGCGCG) and d(ATATAT) differently. Although these observations are consistent with the proposal of Kuwahara and Sugiura (16,17) that the bithiazole is partially responsible for the sequence selectivity of the drug, it is also possible that the sequence-dependent alterations in the bithiazole are secondary to sequence-specific modes of binding induced by the metalbinding site.…”

“…In contrast, the structural features of Fe-BLM responsible for the sequence and chemical specificity of the DNA degradation reaction remain largely obscure. Indeed, there have been reports implicating almost every region of the Fe-BLM molecule, including the C-terminal bithiazole and dimethylsulfonium groups (15)(16)(17), the N-terminal metal binding site (18 -20), the primary amine of the ␤-aminoalanine residue (21), and the "linker region" that connects the metal binding site with the bithiazole group (22,23), as being responsible, at least in part, for the sequence selectivity of Fe-BLM-mediated DNA degradation. While many of these reports appear to provide conflicting results, the one requirement from all but one (24) of these studies is that for sequencespecific cleavage of DNA to occur, both the metal binding site and bithiazole moiety must be intact.…”

Nucleotide-specific cleavage and minor-groove interaction of DNA with esperamicin antitumor antibiotics.

“…6) and suggests an orientation of the diyne-ene perpendicular to the plane of the base pairs in the helix. Pretreatment with distamycin A results in a large change in the sequence-specific DNA cleavage mode of bleomycin, which binds in the minor groove of B-DNA (8,27). In the bleomycin-DNA interaction, the 2-amino group of guanine adjacent to the 5' side of the cleaved pyrimidine is a key element of the specific 5'-GC-3' or 5'-GT-3' recognition (27).…”

“…Recently, a minor-groove interaction model of metallobleomycin in the DNA helix was developed by computer-constructed model building (8). In contrast, neocarzinostatin is itself converted into a diradical that directly attacks the deoxyribose of mainly thymidylate residues in DNA (9)(10)(11)(12)(13)(14).…”

Crystal structure of DNA-bound Co(III)·bleomycin B 2 : Insights on intercalation and minor groove binding

“…The mode of interaction of the bithiazole with DNA, i.e., minor groove binding (31,32) vs. full intercalation and/or partial intercalation, has been the subject of debate. In our studies, we find no evidence of minor groove binding by the bithiazole.…”