Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: implications for interactions with intercalating anticancer agents.

ABSTRACT: DNA topoisomerase II (Top2) is the target of some of the most effective anticancer DNA intercalators. To determine the effect of intercalating ligands at defined positions relative to a known DNA cleavage site for human Top2alpha, we synthesized oligodeoxynucleotides containing single trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide (DE) deoxyadenosine (dA) adducts of known absolute configuration, placed at specific positions in a duplex sequence containing staggered Top2 cleavage sites on both strands. Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible. Our findings demonstrate t

SUBMITTER: Khan QA 

PROVIDER: S-EPMC218786 | biostudies-literature | 2003 Oct

REPOSITORIES: biostudies-literature