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Dumbbell‐shaped Circular Oligonucleotides as Inhibitors of Human Topoisomerase I
Author(s) -
Ng Magdeline Tao Tao,
Li Tianhu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.593.4
Subject(s) - topoisomerase , oligonucleotide , dumbbell , camptothecin , dna supercoil , dna , chemistry , biophysics , sequence (biology) , microbiology and biotechnology , biochemistry , stereochemistry , biology , dna replication , physiology
The interaction of human DNA topoisomerase I (topo 1) with specific sequence oligodeoxynucleotides (ODNs) of different structures was investigated. Certain dumbbell‐shaped circular oligonucleotides containing topoisomerase I‐binding sites and mismatched base pairs in the sequence were designed and synthesized. It was demonstrated that some ODNs used during our investigation inhibited the topo I catalyzed relaxation of supercoiled DNA in an irreversible manner. Our studies demonstrated 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.