| CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY |
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Parallel DNA G-Quadruplex Induced and Stabilized by Curaxin CBL0137 |
| Jing-Wei Kong1,2, Shuo-Xing Dou1,2, Wei Li1,3*, Hui Li4*, and Peng-Ye Wang1,2,3* |
1Laboratory of Soft Matter Physics and Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
2School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
3Songshan Lake Materials Laboratory, Dongguan 523808, China
4School of Systems Science and Institute of Nonequilibrium Systems, Beijing Normal University, Beijing 100875, China
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| Cite this article: |
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Jing-Wei Kong, Shuo-Xing Dou, Wei Li et al 2023 Chin. Phys. Lett. 40 078701 |
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Abstract G-quadruplex (G4) is one of the higher-order DNA structures in guanine-rich sequences which are widely distributed across the genome. Due to their presence in oncogenic promoters and telomeres, G4 DNA structures become the novel targets in anticancer drug designs. Curaxin CBL0137, as an important candidate anticancer drug, can effectively inhibit the growth of multiple cancers. Although there is evidence that anticancer activity of curaxin is associated with its ability to bind DNA and to change the DNA topology, its therapeutic target and the underlying anti-cancer mechanism are still unclear. Here we show, for the first time, that curaxin CBL0137 induces G4 folding from anti-parallel to parallel structures, by single-molecule fluorescence resonance energy transfer technique. More importantly, we find that curaxin CBL0137 promotes G4 folding as well as stabilizes the folded G4 structures with long loops, giving a novel insight into effects of curaxin CBL0137 on DNA structures. Our work provides new ideas for the therapeutic mechanism of curaxin CBL0137 and for designs of new G4-targeting anticancer drugs.
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Received: 24 April 2023
Published: 10 June 2023
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