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Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study

Nucleic acids can adopt non‐duplex topologies, such as G‐quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA‐M2 as a unique fluorescence probe for such studies....

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Autores principales: Shivalingam, Arun, Vyšniauskas, Aurimas, Albrecht, Tim, White, Andrew J. P., Kuimova, Marina K., Vilar, Ramon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991273/
https://www.ncbi.nlm.nih.gov/pubmed/26880483
http://dx.doi.org/10.1002/chem.201504099
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author Shivalingam, Arun
Vyšniauskas, Aurimas
Albrecht, Tim
White, Andrew J. P.
Kuimova, Marina K.
Vilar, Ramon
author_facet Shivalingam, Arun
Vyšniauskas, Aurimas
Albrecht, Tim
White, Andrew J. P.
Kuimova, Marina K.
Vilar, Ramon
author_sort Shivalingam, Arun
collection PubMed
description Nucleic acids can adopt non‐duplex topologies, such as G‐quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA‐M2 as a unique fluorescence probe for such studies. This probe's emission lifetime is highly dependent on the topology of the DNA it interacts with opening up the possibility of carrying out live‐cell imaging studies. Herein, we describe the origin of its fluorescence selectivity for G‐quadruplexes. Cyclic voltammetry predicts that the appended morpholino groups can act as intra‐ molecular photo‐induced electron transfer (PET) quenchers. Photophysical studies show that a delicate balance between this effect and inter‐molecular PET with nucleobases is key to the overall fluorescence enhancement observed upon nucleic acid binding. We utilised computational modelling to demonstrate a conformational dependence of intra‐molecular PET. Finally, we performed orthogonal studies with a triangulenium compound, in which the morpholino groups were removed, and demonstrated that this change inverts triangulenium fluorescence selectivity from G‐quadruplex to duplex DNA, thus highlighting the importance of fine tuning the molecular structure not only for target affinity, but also for fluorescence response.
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spelling pubmed-49912732016-09-06 Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study Shivalingam, Arun Vyšniauskas, Aurimas Albrecht, Tim White, Andrew J. P. Kuimova, Marina K. Vilar, Ramon Chemistry Full Papers Nucleic acids can adopt non‐duplex topologies, such as G‐quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA‐M2 as a unique fluorescence probe for such studies. This probe's emission lifetime is highly dependent on the topology of the DNA it interacts with opening up the possibility of carrying out live‐cell imaging studies. Herein, we describe the origin of its fluorescence selectivity for G‐quadruplexes. Cyclic voltammetry predicts that the appended morpholino groups can act as intra‐ molecular photo‐induced electron transfer (PET) quenchers. Photophysical studies show that a delicate balance between this effect and inter‐molecular PET with nucleobases is key to the overall fluorescence enhancement observed upon nucleic acid binding. We utilised computational modelling to demonstrate a conformational dependence of intra‐molecular PET. Finally, we performed orthogonal studies with a triangulenium compound, in which the morpholino groups were removed, and demonstrated that this change inverts triangulenium fluorescence selectivity from G‐quadruplex to duplex DNA, thus highlighting the importance of fine tuning the molecular structure not only for target affinity, but also for fluorescence response. John Wiley and Sons Inc. 2016-02-16 2016-03-14 /pmc/articles/PMC4991273/ /pubmed/26880483 http://dx.doi.org/10.1002/chem.201504099 Text en © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Shivalingam, Arun
Vyšniauskas, Aurimas
Albrecht, Tim
White, Andrew J. P.
Kuimova, Marina K.
Vilar, Ramon
Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title_full Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title_fullStr Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title_full_unstemmed Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title_short Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
title_sort trianguleniums as optical probes for g‐quadruplexes: a photophysical, electrochemical, and computational study
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991273/
https://www.ncbi.nlm.nih.gov/pubmed/26880483
http://dx.doi.org/10.1002/chem.201504099
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