title: Camptothecins as probes of the microenvironments of topoisomerase I--DNA complexes.
abstract: By uncoupling the cleavage and ligation reactions of DNA oligonucleotides mediated by topoisomerase I, it has been possible to demonstrate modification of DNA oligonucleotide structure by the enzyme. These modifications indicate an unusual flexibility inherent in the behavior of topoisomerase I and may reflect some of the cellular roles played by the enzyme. The ability of individual camptothecin analogues to inhibit these modification processes differentially provides insight into the relative nature of the microenvironments present. To the extent that these enzyme-mediated structural modifications do constitute models of cellular roles for the enzyme, the observed differential inhibition also provides a potential strategy for assessing the function and importance of such modifications.
authors.affiliation: Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA. sidhecht@virginia.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000818:Animals; D001483:Base Sequence; D002166:Camptothecin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin