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

Nature Communications
Arun ShivalingamRamon Vilar

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.

References

Feb 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·L V JohnsonL B Chen
May 15, 2001·Chemistry : a European Journal·B W Laursen, F C Krebs
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Adam Siddiqui-JainLaurence H Hurley
Feb 20, 2003·Journal of the American Chemical Society·Jóhannes ReynissonJonathan B Chaires
Feb 9, 2005·Biochemistry·Arti PothukuchySean M Kerwin
Sep 8, 2007·Biochimie·Anne De CianJean-Louis Mergny
Nov 6, 2007·Biophysical Journal·Michelle A DigmanEnrico Gratton
Nov 4, 2008·Journal of the American Chemical Society·Raphaël RodriguezShankar Balasubramanian
Feb 28, 2009·PloS One·Lars SchmiedebergAdrian Bird
Apr 2, 2011·Nature Reviews. Drug Discovery·Shankar BalasubramanianStephen Neidle
Jul 27, 2011·Chemical Society Reviews·Gavin W Collie, Gary N Parkinson
Feb 1, 2012·Nature Methods·Ulrike SchnellBen N G Giepmans
Feb 7, 2012·Nature Chemical Biology·Raphaël RodriguezStephen P Jackson
Aug 14, 2012·Topics in Current Chemistry·Eric LargyMarie-Paule Teulade-Fichou
Feb 9, 2013·The Journal of Physical Chemistry. a·Erling ThyrhaugBo W Laursen
Feb 21, 2013·Nature Chemistry·Giulia BiffiShankar Balasubramanian
Feb 27, 2013·Chembiochem : a European Journal of Chemical Biology·Balayeshwanth R VummidiNathan W Luedtke
May 15, 2013·PloS One·Badri P MaliwalIgnacy Gryczynski
Jul 11, 2013·Journal of Biomedical Optics·Ting-Yuan TsengTa-Chau Chang
Oct 29, 2013·Nucleic Acids Research·Alexander HendersonPeter M Lansdorp
Jun 10, 2015·Journal of the American Chemical Society·Aurélien LaguerreDavid Monchaud

❮ Previous
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Citations

Feb 4, 2016·Journal of Medicinal Chemistry·Stephen Neidle
Jan 23, 2016·Journal of the American Chemical Society·Antoine WallabregueJerome Lacour
Jun 9, 2016·Journal of Inorganic Biochemistry·Sofia GamaAntónio Paulo
Aug 11, 2016·Journal of the American Chemical Society·Shuo-Bin ChenJia-Heng Tan
Sep 7, 2016·Biochimica Et Biophysica Acta. General Subjects·Sheng LinDik-Lung Ma
Feb 23, 2017·Nature Reviews. Molecular Cell Biology·Robert Hänsel-HertschShankar Balasubramanian
Jan 27, 2017·Chemistry : a European Journal·Dounia SaadallahDavid Monchaud
Apr 15, 2017·Chemistry : a European Journal·Dora M RăsădeanG Dan Pantoş
Feb 5, 2016·Chemistry : a European Journal·Cui-Xia XuPeter Z Qin
Jun 28, 2017·Chemical Communications : Chem Comm·Özden KaracaFritz E Kühn
Dec 4, 2015·Organic & Biomolecular Chemistry·Ilkay BoraBo W Laursen
Mar 30, 2016·Organic & Biomolecular Chemistry·Sushree Prangya Priyadarshinee PanyP I Pradeepkumar
Jun 2, 2017·Chembiochem : a European Journal of Chemical Biology·Sudeshna MannaSeergazhi G Srivatsan
Dec 7, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia Rizeq, Savvas N Georgiades
Mar 8, 2018·ChemMedChem·Ana Rita DuarteAlexandra Paulo
Apr 27, 2018·Chemistry : a European Journal·Irene Hernández DelgadoJérôme Lacour
Dec 5, 2018·Nature Nanotechnology·Binoy Paulose NadappuramJoshua B Edel
Feb 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pallavi ChilkaBhaskar Datta
Dec 28, 2018·Nucleic Acids Research·Anita KotarJanez Plavec
May 21, 2019·Nucleic Acids Research·Ashok NuthanakantiSeergazhi G Srivatsan
Sep 2, 2017·Current Protocols in Cell Biology·Souheila AmorDavid Monchaud
Jan 7, 2020·Chemical Communications : Chem Comm·Federica RaguseoMarco Di Antonio
Apr 4, 2017·Angewandte Chemie·Soichiro NakatsukaTakuji Hatakeyama
Nov 18, 2017·Angewandte Chemie·Stephane BandeiraRamon Vilar
May 7, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Sabrina ValettiIlse Manet
Sep 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ting-Yuan TsengTa-Chau Chang
Sep 14, 2018·RSC Advances·Sudeshna Manna, Seergazhi G Srivatsan
Jul 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mubarak I UmarChun Kit Kwok
Apr 22, 2020·Nature Reviews. Molecular Cell Biology·Dhaval VarshneyShankar Balasubramanian
Jan 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Sheng LinDik-Lung Ma
Mar 22, 2016·Chemistry : a European Journal·Lena HahnLutz H Gade
Sep 22, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Natalia BustoBegoña García
Jul 22, 2020·Nature Chemistry·Marco Di AntonioShankar Balasubramanian

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Methods Mentioned

BETA
nuclear magnetic resonance
light scattering
Assay

Software Mentioned

DAOTA
ADOTA
Tri2
TCSPC
MatLab

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