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; Ramon Vilar

doi:10.1038/ncomms9178

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, Ramon Vilar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	8178
Pages (from-to)	1-10
Journal	Nature Communications
Volume	6
Early online date	9 Sept 2015
DOIs	https://doi.org/10.1038/ncomms9178
Publication status	Published - Sept 2015

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The interactions between a_SHIVALINGAM_Acc25Jul2015_GOLD VoR(CC BY)Final published version, 1.03 MBLicence: CC BY

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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.",

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AU - Vyšniauskas, Aurimas

AU - Suhling, Klaus

AU - Kuimova, Marina K.

AU - Vilar, Ramon

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

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