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- W4308741414 abstract "DNA topoisomerase I was found to be highly abundant in fast-proliferating tumor cells and is a potential target for anticancer therapy. A series of G-quadruplex-containing oligodeoxynucleotides (ODNs) were designed and used as inhibitors of DNA topoisomerase I. It was demonstrated that ODNs with G-quadruplexes can efficiently inhibit the supercoiled DNA relaxation reaction catalyzed by DNA topoisomerase I. Compared with the other conformations, the parallel propeller-type G-quadruplex was the most efficient DNA topoisomerase I inhibitor. Further studies revealed that integrating G-quadruplexes with duplexes to form quadruplex-duplex hybrids could significantly improve the inhibition efficiency. In addition, a circular ODN that consists of a G-quadruplex motif and DNA topoisomerase I binding site was synthesized and used as a DNA topoisomerase I inhibitor. The results showed that the particularly designed circular ODN displayed high inhibitory efficiency on the activity of DNA topoisomerase I with an IC50 value of 54.8 nM. Moreover, the circular ODN exhibited excellent thermal stability and nuclease resistance. Considering the low cytotoxicity of DNA-based biopharmaceuticals, the design strategy and results reported in this study may shed new light on nucleic acid-based DNA topoisomerase I inhibitor construction for potential anticancer drugs." @default.
- W4308741414 created "2022-11-15" @default.
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- W4308741414 date "2022-12-01" @default.
- W4308741414 modified "2023-09-23" @default.
- W4308741414 title "G-quadruplex-containing oligodeoxynucleotides as DNA topoisomerase I inhibitors" @default.
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- W4308741414 doi "https://doi.org/10.1016/j.ijbiomac.2022.11.025" @default.
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