Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand

The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein–protein interaction of Survivin and its functionally relevant binding partner Histone H...

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Autores principales: Vallet, Cecilia, Aschmann, Dennis, Beuck, Christine, Killa, Matthias, Meiners, Annika, Mertel, Marcel, Ehlers, Martin, Bayer, Peter, Schmuck, Carsten, Giese, Michael, Knauer, Shirley K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155087/
https://www.ncbi.nlm.nih.gov/pubmed/31916356
http://dx.doi.org/10.1002/anie.201915400
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author Vallet, Cecilia
Aschmann, Dennis
Beuck, Christine
Killa, Matthias
Meiners, Annika
Mertel, Marcel
Ehlers, Martin
Bayer, Peter
Schmuck, Carsten
Giese, Michael
Knauer, Shirley K.
author_facet Vallet, Cecilia
Aschmann, Dennis
Beuck, Christine
Killa, Matthias
Meiners, Annika
Mertel, Marcel
Ehlers, Martin
Bayer, Peter
Schmuck, Carsten
Giese, Michael
Knauer, Shirley K.
author_sort Vallet, Cecilia
collection PubMed
description The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein–protein interaction of Survivin and its functionally relevant binding partner Histone H3. Ligand L1 is based on the guanidiniocarbonyl pyrrole cation and serves as a highly specific anion binder in order to target the interaction between Survivin and Histone H3. NMR titration confirmed binding of L1 to Survivin's Histone H3 binding site. The inhibition of the Survivin–Histone H3 interaction and consequently a reduction of cancer cell proliferation were demonstrated by microscopic and cellular assays.
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spelling pubmed-71550872020-04-15 Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand Vallet, Cecilia Aschmann, Dennis Beuck, Christine Killa, Matthias Meiners, Annika Mertel, Marcel Ehlers, Martin Bayer, Peter Schmuck, Carsten Giese, Michael Knauer, Shirley K. Angew Chem Int Ed Engl Communications The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein–protein interaction of Survivin and its functionally relevant binding partner Histone H3. Ligand L1 is based on the guanidiniocarbonyl pyrrole cation and serves as a highly specific anion binder in order to target the interaction between Survivin and Histone H3. NMR titration confirmed binding of L1 to Survivin's Histone H3 binding site. The inhibition of the Survivin–Histone H3 interaction and consequently a reduction of cancer cell proliferation were demonstrated by microscopic and cellular assays. John Wiley and Sons Inc. 2020-01-28 2020-03-27 /pmc/articles/PMC7155087/ /pubmed/31916356 http://dx.doi.org/10.1002/anie.201915400 Text en © 2020 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/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Vallet, Cecilia
Aschmann, Dennis
Beuck, Christine
Killa, Matthias
Meiners, Annika
Mertel, Marcel
Ehlers, Martin
Bayer, Peter
Schmuck, Carsten
Giese, Michael
Knauer, Shirley K.
Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title_full Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title_fullStr Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title_full_unstemmed Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title_short Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand
title_sort functional disruption of the cancer‐relevant interaction between survivin and histone h3 with a guanidiniocarbonyl pyrrole ligand
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155087/
https://www.ncbi.nlm.nih.gov/pubmed/31916356
http://dx.doi.org/10.1002/anie.201915400
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