Nick-containing oligonucleotides as human topoisomerase I inhibitors.

A series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites were designed. The interactions between these oligonucleotides and human topoisomerase I were investigated and the most efficient one among them has displayed IC(50) value of 6.3 nM. Our studies have also demonstrated that the position of the nick as well as the length of the oligonucleotides were crucial factors for the inhibition of this nuclear enzyme.