Dumbbell-shaped circular oligonucleotides as inhibitors of human topoisomerase I.

A dumbbell-shaped circular oligonucleotide containing topoisomerase I-binding sites and two mismatched base pairs in its sequence has been designed and synthesized. Our further studies demonstrate that this particularly designed oligonucleotide displays an IC(50) value of 9 nM in its inhibition on the activity of human topoisomerase I, a magnitude smaller than that of camptothecin, an anticancer drug currently in clinical use.