To achieve a sequence-specific DNA cleavage by topoisomerase I, derivatives of the
antitumor drug camptothecin have been covalently linked to triple helix-forming
oligonucleotides that bind in a sequence-specific manner to the major groove of double-
helical DNA. Triplex formation at the target sequence positions the drug selectively at the
triplex site, thereby stimulating topoisomerase I-mediated DNA cleavage at this site. In a
continuous effort to optimize this strategy, a broad set of conjugates consisting of (i) 16–20 …