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The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy

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Listed:
  • Arun Shivalingam

    (Imperial College London)

  • M. Angeles Izquierdo

    (Imperial College London)

  • Alix Le Marois

    (King’s College London)

  • Aurimas Vyšniauskas

    (Imperial College London)

  • Klaus Suhling

    (King’s College London)

  • Marina K. Kuimova

    (Imperial College London)

  • Ramon Vilar

    (Imperial College London)

Abstract

Guanine-rich oligonucleotides can fold into quadruple-stranded helical structures known as G-quadruplexes. Mounting experimental evidence has gathered suggesting that these non-canonical nucleic acid structures form in vivo and play essential biological roles. However, to date, there are no small-molecule optical probes to image G-quadruplexes in live cells. Herein, we report the design and development of a small fluorescent molecule, which can be used as an optical probe for G-quadruplexes. We demonstrate that the fluorescence lifetime of this new probe changes considerably upon interaction with different nucleic acid topologies. Specifically, longer fluorescence lifetimes are observed in vitro for G-quadruplexes than for double- and single-stranded nucleic acids. Cellular studies confirm that this molecule is cell permeable, has low cytotoxicity and localizes primarily in the cell nucleus. Furthermore, using fluorescence lifetime imaging microscopy, live-cell imaging suggests that the probe can be used to study the interaction of small molecules with G-quadruplexes in vivo.

Suggested Citation

  • Arun Shivalingam & M. Angeles Izquierdo & Alix Le Marois & Aurimas Vyšniauskas & Klaus Suhling & Marina K. Kuimova & Ramon Vilar, 2015. "The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9178
    DOI: 10.1038/ncomms9178
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