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Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle

Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterizatio...

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Autores principales: Domarco, Olaya, Kieler, Claudia, Pirker, Christine, Dinhof, Carina, Englinger, Bernhard, Reisecker, Johannes M., Timelthaler, Gerald, García, Marcos D., Peinador, Carlos, Keppler, Bernhard K., Berger, Walter, Terenzi, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563712/
https://www.ncbi.nlm.nih.gov/pubmed/31002438
http://dx.doi.org/10.1002/anie.201900934
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author Domarco, Olaya
Kieler, Claudia
Pirker, Christine
Dinhof, Carina
Englinger, Bernhard
Reisecker, Johannes M.
Timelthaler, Gerald
García, Marcos D.
Peinador, Carlos
Keppler, Bernhard K.
Berger, Walter
Terenzi, Alessio
author_facet Domarco, Olaya
Kieler, Claudia
Pirker, Christine
Dinhof, Carina
Englinger, Bernhard
Reisecker, Johannes M.
Timelthaler, Gerald
García, Marcos D.
Peinador, Carlos
Keppler, Bernhard K.
Berger, Walter
Terenzi, Alessio
author_sort Domarco, Olaya
collection PubMed
description Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in‐cell tracking of a Pt(2)L(2) metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4‐rich regions. SCC co‐localizes with epitopes of the quadruplex‐specific antibody BG4 and replaces other well‐known G4 stabilizers. Moreover, the photophysical changes accompanying the metallacycle binding to G4s in solution (fluorescence quenching, absorption enhancement) also take place intracellularly, allowing its subcellular interaction tracking.
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spelling pubmed-65637122019-06-20 Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle Domarco, Olaya Kieler, Claudia Pirker, Christine Dinhof, Carina Englinger, Bernhard Reisecker, Johannes M. Timelthaler, Gerald García, Marcos D. Peinador, Carlos Keppler, Bernhard K. Berger, Walter Terenzi, Alessio Angew Chem Int Ed Engl Communications Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in‐cell tracking of a Pt(2)L(2) metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4‐rich regions. SCC co‐localizes with epitopes of the quadruplex‐specific antibody BG4 and replaces other well‐known G4 stabilizers. Moreover, the photophysical changes accompanying the metallacycle binding to G4s in solution (fluorescence quenching, absorption enhancement) also take place intracellularly, allowing its subcellular interaction tracking. John Wiley and Sons Inc. 2019-05-08 2019-06-11 /pmc/articles/PMC6563712/ /pubmed/31002438 http://dx.doi.org/10.1002/anie.201900934 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Communications
Domarco, Olaya
Kieler, Claudia
Pirker, Christine
Dinhof, Carina
Englinger, Bernhard
Reisecker, Johannes M.
Timelthaler, Gerald
García, Marcos D.
Peinador, Carlos
Keppler, Bernhard K.
Berger, Walter
Terenzi, Alessio
Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title_full Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title_fullStr Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title_full_unstemmed Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title_short Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal Pt(II) Metallacycle
title_sort subcellular duplex dna and g‐quadruplex interaction profiling of a hexagonal pt(ii) metallacycle
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563712/
https://www.ncbi.nlm.nih.gov/pubmed/31002438
http://dx.doi.org/10.1002/anie.201900934
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