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

Arun Shivalingam, M. Angeles Izquierdo, Alix Le Marois, Aurimas Vyšniauskas, Klaus Suhling, Marina K. Kuimova () and Ramon Vilar ()
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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

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9178

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DOI: 10.1038/ncomms9178

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