Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9178
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Funding
- Engineering and Physical Sciences Research Council of the UK [EP/I003983/1, EP/H005285/1]
- European Commission
- Engineering and Physical Sciences Research Council [EP/I003983/1, 1231179, EP/K039946/1, EP/H005285/1] Funding Source: researchfish
- Medical Research Council [MR/K015664/1] Funding Source: researchfish
- EPSRC [EP/I003983/1, EP/H005285/1, EP/K039946/1] Funding Source: UKRI
- MRC [MR/K015664/1] Funding Source: UKRI
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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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