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.
Chua
Sock Teng
ST
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Walk, Blk 5 Level 3, Nanyang Technological University, Singapore 637616, Singapore.
Quek
Ngee Mien
NM
Li
Ming
M
Ng
Magdeline Tao Tao
MT
Yuan
Weixing
W
Chua
May Ling
ML
Guo
Juanjuan
J
Koh
Li Eng
LE
Ye
Ruijuan
R
Li
Tianhu
T
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
D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D059004:Topoisomerase I Inhibitors; D004247:DNA