title: Nick-containing oligonucleotides as human topoisomerase I inhibitors.
abstract: 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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Walk, Blk 5 Level 3, Nanyang Technological University, Singapore 637616, Singapore.
authors.forename: Sock Teng
authors.initials: ST
authors.lastname: Chua
authors.forename: Ngee Mien
authors.initials: NM
authors.lastname: Quek
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Magdeline Tao Tao
authors.initials: MT
authors.lastname: Ng
authors.forename: Weixing
authors.initials: W
authors.lastname: Yuan
authors.forename: May Ling
authors.initials: ML
authors.lastname: Chua
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Guo
authors.forename: Li Eng
authors.initials: LE
authors.lastname: Koh
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Ye
authors.forename: Tianhu
authors.initials: T
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D002467:Cell Nucleus / Q000201:enzymology; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D013379:Substrate Specificity; D059004:Topoisomerase I Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D059004:Topoisomerase I Inhibitors; D004247:DNA