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Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding

Author

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  • Wenting Liu

    (Sun Yat-Sen University)

  • Yi-Fang Zhong

    (Sun Yat-Sen University
    South China Agricultural University)

  • Liu-Yi Liu

    (Sun Yat-Sen University)

  • Chu-Tong Shen

    (Sun Yat-Sen University)

  • Wenjuan Zeng

    (Chinese Academy of Sciences)

  • Fuyi Wang

    (Chinese Academy of Sciences)

  • Danzhou Yang

    (Purdue University)

  • Zong-Wan Mao

    (Sun Yat-Sen University
    South China Agricultural University)

Abstract

DNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripod‒Tel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod–Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5ʹ-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0–1.0. After adding more Pt-tripod, the Pt-tripod binds the 3ʹ-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3ʹ-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes.

Suggested Citation

  • Wenting Liu & Yi-Fang Zhong & Liu-Yi Liu & Chu-Tong Shen & Wenjuan Zeng & Fuyi Wang & Danzhou Yang & Zong-Wan Mao, 2018. "Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05810-4
    DOI: 10.1038/s41467-018-05810-4
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    Cited by:

    1. Kai-Bo Wang & Yushuang Liu & Jinzhu Li & Chengmei Xiao & Yingying Wang & Wei Gu & Yipu Li & Yuan-Zheng Xia & Tingdong Yan & Ming-Hua Yang & Ling-Yi Kong, 2022. "Structural insight into the bulge-containing KRAS oncogene promoter G-quadruplex bound to berberine and coptisine," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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