Unveiling Englerin A as a modulator of L-type calcium channels

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Tiago
Data de Publicação: 2016
Outros Autores: Sieglitz, Florian, Somovilla, Víctor J., Cal, Pedro M.S.D., Galione, Antony, Corzana, Francisco, Bernardes, Gonçalo J. L.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/53072
Resumo: © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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spelling Unveiling Englerin A as a modulator of L-type calcium channelsChemical biologyMolecular recognitionNatural productsTarget predictionVoltage-gated calcium channels© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The voltage-dependent L-type Ca(2+) channel was identified as a macromolecular target for (-)-englerin A. This finding was reached by using an unprecedented ligand-based prediction platform and the natural product piperlongumine as a pharmacophore probe. (-)-Englerin A features high substructure dissimilarity to known ligands for voltage-dependent Ca(2+) channels, selective binding affinity for the dihydropyridine site, and potent modulation of calcium signaling in muscle cells and vascular tissue. The observed activity was rationalized at the atomic level by molecular dynamics simulations. Experimental confirmation of this hitherto unknown macromolecular target expands the bioactivity space for this natural product and corroborates the effectiveness of chemocentric computational methods for prioritizing target-based screens and identifying binding counterparts of complex natural products.We thank FCT Portugal (FCT Investigator to G.J.L.B. and Postdoctoral Fellowship SFRH/BPD/103172/2014 to P.M.S.D.C.), the European Commission (Marie-Curie CIG to G.J.L.B.), DFG (SI 2117/1-1 to F.S.), the EPSRC and MRC for financial support.John Wiley & Sons, Inc.Repositório da Universidade de LisboaRodrigues, TiagoSieglitz, FlorianSomovilla, Víctor J.Cal, Pedro M.S.D.Galione, AntonyCorzana, FranciscoBernardes, Gonçalo J. L.2022-05-19T14:32:26Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53072engAngew Chem Int Ed Engl. 2016 Sep 5;55(37):11077-811433-785110.1002/anie.2016043361521-3773info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:58:38Zoai:repositorio.ul.pt:10451/53072Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:01.770348Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Unveiling Englerin A as a modulator of L-type calcium channels
title Unveiling Englerin A as a modulator of L-type calcium channels
spellingShingle Unveiling Englerin A as a modulator of L-type calcium channels
Rodrigues, Tiago
Chemical biology
Molecular recognition
Natural products
Target prediction
Voltage-gated calcium channels
title_short Unveiling Englerin A as a modulator of L-type calcium channels
title_full Unveiling Englerin A as a modulator of L-type calcium channels
title_fullStr Unveiling Englerin A as a modulator of L-type calcium channels
title_full_unstemmed Unveiling Englerin A as a modulator of L-type calcium channels
title_sort Unveiling Englerin A as a modulator of L-type calcium channels
author Rodrigues, Tiago
author_facet Rodrigues, Tiago
Sieglitz, Florian
Somovilla, Víctor J.
Cal, Pedro M.S.D.
Galione, Antony
Corzana, Francisco
Bernardes, Gonçalo J. L.
author_role author
author2 Sieglitz, Florian
Somovilla, Víctor J.
Cal, Pedro M.S.D.
Galione, Antony
Corzana, Francisco
Bernardes, Gonçalo J. L.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Rodrigues, Tiago
Sieglitz, Florian
Somovilla, Víctor J.
Cal, Pedro M.S.D.
Galione, Antony
Corzana, Francisco
Bernardes, Gonçalo J. L.
dc.subject.por.fl_str_mv Chemical biology
Molecular recognition
Natural products
Target prediction
Voltage-gated calcium channels
topic Chemical biology
Molecular recognition
Natural products
Target prediction
Voltage-gated calcium channels
description © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01T00:00:00Z
2022-05-19T14:32:26Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/53072
url http://hdl.handle.net/10451/53072
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Angew Chem Int Ed Engl. 2016 Sep 5;55(37):11077-81
1433-7851
10.1002/anie.201604336
1521-3773
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons, Inc.
publisher.none.fl_str_mv John Wiley & Sons, Inc.
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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