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Enabling programmable dynamic DNA chemistry using small-molecule DNA binders

Author

Listed:
  • Junpeng Xu

    (Sichuan University
    Brock University)

  • Guan Alex Wang

    (Sichuan University)

  • Lu Gao

    (Sichuan University)

  • Lang Wu

    (Sichuan University)

  • Qian Lei

    (Sichuan University)

  • Hui Deng

    (Sichuan University)

  • Feng Li

    (Sichuan University
    Brock University
    Sichuan University)

Abstract

The binding of small molecules to the double helical structure of DNA, through either intercalation or minor groove binding, may significantly alter the stability and functionality of DNA, which is a fundamental basis for many therapeutic and sensing applications. Here, we report that small-molecule DNA binders can also be used to program reaction pathways of a dynamic DNA reaction, where DNA strand displacement can be tuned quantitatively according to the affinity, charge, and concentrations of a given DNA binder. The binder-induced nucleic acid strand displacement (BIND) thus enables innovative technologies to accelerate the discovery and characterization of bioactive small molecules. Specifically, we demonstrate the comprehensive characterization of existing and newly discovered DNA binders, where critical parameters for binding affinity and sequence selectivity can be obtained in a single, unbiased molecular platform without the need for any specialized equipment. We also engineer a tandem BIND system as a high-throughput screening assay for discovering DNA binders, through which 8 DNA binders were successfully discovered from a library of 700 compounds.

Suggested Citation

  • Junpeng Xu & Guan Alex Wang & Lu Gao & Lang Wu & Qian Lei & Hui Deng & Feng Li, 2023. "Enabling programmable dynamic DNA chemistry using small-molecule DNA binders," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40032-3
    DOI: 10.1038/s41467-023-40032-3
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    References listed on IDEAS

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    1. Bernard Yurke & Andrew J. Turberfield & Allen P. Mills & Friedrich C. Simmel & Jennifer L. Neumann, 2000. "A DNA-fuelled molecular machine made of DNA," Nature, Nature, vol. 406(6796), pages 605-608, August.
    2. Kakishi Uno & Nagisa Sugimoto & Yoshikatsu Sato, 2021. "N-aryl pyrido cyanine derivatives are nuclear and organelle DNA markers for two-photon and super-resolution imaging," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    3. Andreas S. Biebricher & Iddo Heller & Roel F. H. Roijmans & Tjalle P. Hoekstra & Erwin J. G. Peterman & Gijs J. L. Wuite, 2015. "The impact of DNA intercalators on DNA and DNA-processing enzymes elucidated through force-dependent binding kinetics," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
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