Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers

Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB b...

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Authors: Dallavalle, Sabrina, Mattio, Luce M., Artali, Roberto, Musso, Loana, Aviñó, Anna, Fàbrega, Carme, Eritja Casadellà, Ramón, Gargallo, Raimundo, Mazzini, Stefania
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/244921
Online Access:http://hdl.handle.net/10261/244921
Access Level:Open access
Keyword:Curaxin
NMR spectroscopy
Circular dichroism
G-quadruplex
Molecular modeling
DNA interactions
c-myc
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spelling Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA OligomersDallavalle, SabrinaMattio, Luce M.Artali, RobertoMusso, LoanaAviñó, AnnaFàbrega, CarmeEritja Casadellà, RamónGargallo, RaimundoMazzini, StefaniaCuraxinNMR spectroscopyCircular dichroismG-quadruplexMolecular modelingDNA interactionsc-mycCuraxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed 1H and 31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.This research was funded by PIANO DI SOSTEGNO ALLA RICERCA 2020—Linea 2 azione B (DEFENS) and by the Spanish Ministerio de Ciencia e Innnvacion (PID2019-107158GB-I00) and recognition from the Autonomous Catalan government (2017SGR114).Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia e Innovación (España)Eritja Casadellà, Ramón [0000-0001-5383-9334]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/244921reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107158GB-I00https://doi.org/10.3390/ijms22126476Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2449212026-05-22T06:33:51Z
dc.title.none.fl_str_mv Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
title Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
spellingShingle Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
Dallavalle, Sabrina
Curaxin
NMR spectroscopy
Circular dichroism
G-quadruplex
Molecular modeling
DNA interactions
c-myc
title_short Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
title_full Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
title_fullStr Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
title_full_unstemmed Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
title_sort Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
dc.creator.none.fl_str_mv Dallavalle, Sabrina
Mattio, Luce M.
Artali, Roberto
Musso, Loana
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
Gargallo, Raimundo
Mazzini, Stefania
author Dallavalle, Sabrina
author_facet Dallavalle, Sabrina
Mattio, Luce M.
Artali, Roberto
Musso, Loana
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
Gargallo, Raimundo
Mazzini, Stefania
author_role author
author2 Mattio, Luce M.
Artali, Roberto
Musso, Loana
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
Gargallo, Raimundo
Mazzini, Stefania
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Eritja Casadellà, Ramón [0000-0001-5383-9334]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Curaxin
NMR spectroscopy
Circular dichroism
G-quadruplex
Molecular modeling
DNA interactions
c-myc
topic Curaxin
NMR spectroscopy
Circular dichroism
G-quadruplex
Molecular modeling
DNA interactions
c-myc
description Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed 1H and 31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
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/10261/244921
url http://hdl.handle.net/10261/244921
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107158GB-I00
https://doi.org/10.3390/ijms22126476
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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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score 15,81155

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