Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry

8 pags, 3 figs, 2 pags, 1 sch

Detalles Bibliográficos
Autores: López-Senín, P., Gómez-Pinto, Irene, Grandas, Anna, Marchán, V.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/254415
Acceso en línea:http://hdl.handle.net/10261/254415
Access Level:acceso abierto
Palabra clave:Combinatorial chemistry
Molecular recognition
RNA ligands
RNA structures
Template synthesis
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repository_id_str
spelling Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistryLópez-Senín, P.Gómez-Pinto, IreneGrandas, AnnaMarchán, V.Combinatorial chemistryMolecular recognitionRNA ligandsRNA structuresTemplate synthesis8 pags, 3 figs, 2 pags, 1 schWe describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exona 10-5′-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosomea 17 (FTDP-17). A series of ligands that combine the small aminoglycoside neamine and heteroaromatic moieties (azaquinolone and two acridines) have been identified by using DCC. These compounds effectively bind the stem-loop RNA target (the concentration required for 50% RNA response (EC50): 2-58μM), as determined by fluorescence titration experiments. Importantly, most of them are able to stabilize both the wild-type and the +3 and +14 mutated sequences associated with the development of FTDP-17 without producing a significant change in the overall structure of the RNA (as analyzed by circular dichroism (CD) spectroscopy), which is a key factor for recognition by the splicing regulatory machinery. A good correlation has been found between the affinity of the ligands for the target and their ability to stabilize the RNA secondary structure. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This work was supported by funds from the Spanish Ministerio de Educación y Ciencia (grant no. CTQ 2007-68014-01/02), the Generalitat de Catalunya (grant no. 2005SGR-693 and the Xarxa de Referència de Biotecnologia), and the Programa d’Intensificació de la Recerca (Universitat de Barcelona). P.L.-S. received a fellowship from the Ministerio de Educación y Ciencia.John Wiley & SonsMinisterio de Educación y Ciencia (España)Generalitat de CatalunyaUniversidad de BarcelonaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120112021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/254415reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1002/chem.201002065Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2544152026-05-22T06:33:51Z
dc.title.none.fl_str_mv Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
title Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
spellingShingle Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
López-Senín, P.
Combinatorial chemistry
Molecular recognition
RNA ligands
RNA structures
Template synthesis
title_short Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
title_full Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
title_fullStr Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
title_full_unstemmed Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
title_sort Identification of ligands for the Tau exona 10 splicing regulatory element RNA by using dynamic combinatorial chemistry
dc.creator.none.fl_str_mv López-Senín, P.
Gómez-Pinto, Irene
Grandas, Anna
Marchán, V.
author López-Senín, P.
author_facet López-Senín, P.
Gómez-Pinto, Irene
Grandas, Anna
Marchán, V.
author_role author
author2 Gómez-Pinto, Irene
Grandas, Anna
Marchán, V.
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Generalitat de Catalunya
Universidad de Barcelona
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Combinatorial chemistry
Molecular recognition
RNA ligands
RNA structures
Template synthesis
topic Combinatorial chemistry
Molecular recognition
RNA ligands
RNA structures
Template synthesis
description 8 pags, 3 figs, 2 pags, 1 sch
publishDate 2011
dc.date.none.fl_str_mv 2011
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/10261/254415
url http://hdl.handle.net/10261/254415
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1002/chem.201002065
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 15,811543

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