Inhibition of topoisomerase I by anthracycline antibiotics: evidence for general inhibition of topoisomerase I by DNA-binding agents.
Inhibition of eukaryotic topoisomerase I by daunomycin and structurally modified daunomycin analogues is demonstrated. These studies suggest that binding of the drug to DNA, at low ratios of drug to base pairs of DNA, is sufficient for inhibition that is nonspecific, i.e., inhibition that does not involve the trapping of covalent DNA-topoisomerase I cleavable complexes. Inhibition of numerous DNA-processing enzymes by DNA-binding agents is also implicated.
Crow
R T
RT
Sterling Laboratory of Chemistry, Yale University, New Haven, Connecticut 06511.
Crothers
D M
DM
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000903:Antibiotics, Antineoplastic; D059004:Topoisomerase I Inhibitors; D004247:DNA; D003630:Daunorubicin