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.
Li
Xinming
X
Department of Chemistry, 3 Science Drive 3, National University of Singapore, Singapore, Singapore.
Tao Ng
Magdeline Tao
MT
Wang
Yifan
Y
Liu
Xiaoqian
X
Li
Tianhu
T
D000838:Anions; D020137:Base Pair Mismatch; D001483:Base Sequence; D001665:Binding Sites; D002166:Camptothecin / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*
D000838:Anions; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin