G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.

Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for regulating key biological activities and processes as transcription, replication, and repair in living cells. The information regarding their role and use as therapeutic drug target...

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Detalles Bibliográficos
Autores: Cebrián, Rubén, Belmonte-Reche, Efres, Pirota, Valentina, Jong, Anne de, Morales, Juan Carlos, Freccero, Mauro, Doria, Filippo, Kuipers, O. P.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/360429
Acceso en línea:http://hdl.handle.net/10261/360429
Access Level:acceso abierto
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spelling G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.Cebrián, RubénBelmonte-Reche, EfresPirota, ValentinaJong, Anne deMorales, Juan CarlosFreccero, MauroDoria, FilippoKuipers, O. P.Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for regulating key biological activities and processes as transcription, replication, and repair in living cells. The information regarding their role and use as therapeutic drug targets in bacteria is still scarce. Here, we tested the biological activity of a G4-DNA ligand library, based on the naphthalene diimide (NDI) pharmacophore, against both Gram-positive and Gram-negative bacteria. For the best compound identified, NDI-10, a different action mechanism was described for Gram-positive or negative bacteria. This asymmetric activity profile could be related to the different prevalence of putative G4-DNA structures in each group, the influence that they can exert on gene expression, and the different roles of the G4 structures in these bacteria, which seem to promote transcription in Gram-positive bacteria and repress transcription in Gram-negatives.This project was financed with the NWA Idea generator program (NWA.1228.191.006, NWO, Dutch Research Council). R.C. was financed by the Ramón-Areces Foundation (Spain) and the NACTAR program (Novel Antibacterial Compounds and Therapies Antagonising Resistance, NWO, Project No. 16433).Peer reviewedFundación Ramón ArecesDutch Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420222024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/360429reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1021/acs.jmedchem.1c01905Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3604292026-05-22T06:33:51Z
dc.title.none.fl_str_mv G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
title G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
spellingShingle G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
Cebrián, Rubén
title_short G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
title_full G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
title_fullStr G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
title_full_unstemmed G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
title_sort G¿Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
dc.creator.none.fl_str_mv Cebrián, Rubén
Belmonte-Reche, Efres
Pirota, Valentina
Jong, Anne de
Morales, Juan Carlos
Freccero, Mauro
Doria, Filippo
Kuipers, O. P.
author Cebrián, Rubén
author_facet Cebrián, Rubén
Belmonte-Reche, Efres
Pirota, Valentina
Jong, Anne de
Morales, Juan Carlos
Freccero, Mauro
Doria, Filippo
Kuipers, O. P.
author_role author
author2 Belmonte-Reche, Efres
Pirota, Valentina
Jong, Anne de
Morales, Juan Carlos
Freccero, Mauro
Doria, Filippo
Kuipers, O. P.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Ramón Areces
Dutch Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for regulating key biological activities and processes as transcription, replication, and repair in living cells. The information regarding their role and use as therapeutic drug targets in bacteria is still scarce. Here, we tested the biological activity of a G4-DNA ligand library, based on the naphthalene diimide (NDI) pharmacophore, against both Gram-positive and Gram-negative bacteria. For the best compound identified, NDI-10, a different action mechanism was described for Gram-positive or negative bacteria. This asymmetric activity profile could be related to the different prevalence of putative G4-DNA structures in each group, the influence that they can exert on gene expression, and the different roles of the G4 structures in these bacteria, which seem to promote transcription in Gram-positive bacteria and repress transcription in Gram-negatives.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/360429
url http://hdl.handle.net/10261/360429
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1021/acs.jmedchem.1c01905
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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