Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer

Selective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. We demonstrate that an imid...

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Detalles Bibliográficos
Autores: Street, Steven T. G., Chin, Donovan N., Hollingworth, Gregory J., Berry, Monica, Morales, Juan Carlos, Galán, M. Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/163349
Acceso en línea:http://hdl.handle.net/10261/163349
Access Level:acceso abierto
Palabra clave:Antitumour agents
Carbohydrates
Drug design
G-quadruplexes
Molecular recognition
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spelling Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ BufferStreet, Steven T. G.Chin, Donovan N.Hollingworth, Gregory J.Berry, MonicaMorales, Juan CarlosGalán, M. CarmenAntitumour agentsCarbohydratesDrug designG-quadruplexesMolecular recognitionSelective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. We demonstrate that an imidazolium‐bearing mannoside‐conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine‐bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI‐38.S.T.G.S.thanksDr.A.Izaac(Novartis)for support withITC, Dr.A.Bailey(Bristol)for use of qPCRand BrisSynBIo(BB/L01386X/1)for use of the NanoDrop UV/Vis spectrophotometer and PlateReader, Dr.A.Leardand the WolfsonBioimagingFacility(BB/L014181/1)for supportwith ConfocalMicroscopy andEPSRCEP/G036764/1for aPhD studentship.M.C.G.thanksthe EPSRCEP/J002542/1and ERC-COG648239 for funding. J.C.M.thanksMinisterio de EconomíayCompetitividad(CTQ2012-35360 andCTQ2015-64275-PPeer reviewedJohn Wiley & SonsConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201820182017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/163349reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201700140Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1633492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
title Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
spellingShingle Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
Street, Steven T. G.
Antitumour agents
Carbohydrates
Drug design
G-quadruplexes
Molecular recognition
title_short Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
title_full Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
title_fullStr Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
title_full_unstemmed Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
title_sort Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer
dc.creator.none.fl_str_mv Street, Steven T. G.
Chin, Donovan N.
Hollingworth, Gregory J.
Berry, Monica
Morales, Juan Carlos
Galán, M. Carmen
author Street, Steven T. G.
author_facet Street, Steven T. G.
Chin, Donovan N.
Hollingworth, Gregory J.
Berry, Monica
Morales, Juan Carlos
Galán, M. Carmen
author_role author
author2 Chin, Donovan N.
Hollingworth, Gregory J.
Berry, Monica
Morales, Juan Carlos
Galán, M. Carmen
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Antitumour agents
Carbohydrates
Drug design
G-quadruplexes
Molecular recognition
topic Antitumour agents
Carbohydrates
Drug design
G-quadruplexes
Molecular recognition
description Selective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. We demonstrate that an imidazolium‐bearing mannoside‐conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine‐bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI‐38.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
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/10261/163349
url http://hdl.handle.net/10261/163349
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201700140
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
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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