Directing Topoisomerase I Mediated DNA Cleavage to Specific Sites by Camptothecin Tethered to Minor- and Major-Groove Ligands

The covalent linkage of a hairpin polyamide, which binds in the minor groove, to camptothecin provides an efficient system to direct topoisomerase I mediated DNA cleavage to specific sites. These conjugates are equally as potent at targeting the enzyme to a single site in a DNA fragment as camptothecin conjugates of ligands that bind in the major groove (triplex-forming oligonucleotides).