Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry

We describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome...

Descripción completa

Detalles Bibliográficos
Autores: López-Senín, Paula, Gómez-Pinto, Irene, Grandas Sagarra, Anna, Marchán Sancho, Vicente
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2011
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/44407
Acceso en línea:https://hdl.handle.net/2445/44407
Access Level:acceso abierto
Palabra clave:Química combinatòria
Bioquímica
RNA
Reconeixement molecular
Combinatorial chemistry
Biochemistry
Molecular recognition
id ES_b772a8d4c2f5ea9862ff1ac5af1db2c1
oai_identifier_str oai:diposit.ub.edu:2445/44407
network_acronym_str ES
network_name_str España
repository_id_str
spelling Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial ChemistryLópez-Senín, PaulaGómez-Pinto, IreneGrandas Sagarra, AnnaMarchán Sancho, VicenteQuímica combinatòriaBioquímicaRNAReconeixement molecularCombinatorial chemistryBiochemistryRNAMolecular recognitionWe describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome 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 (EC(50)): 2-58 μM), 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.Wiley-VCH2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionapplication/pdfhttps://hdl.handle.net/2445/44407Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió preprint del document publicat a: http://dx.doi.org/10.1002/chem.201002065Chemistry-A European Journal, 2011, vol. 17, num. 6, p. 1946-1953http://dx.doi.org/10.1002/chem.201002065(c) Wiley-VCH, 2011info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/444072026-05-27T06:46:51Z
dc.title.none.fl_str_mv Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
title Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
spellingShingle Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
López-Senín, Paula
Química combinatòria
Bioquímica
RNA
Reconeixement molecular
Combinatorial chemistry
Biochemistry
RNA
Molecular recognition
title_short Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
title_full Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
title_fullStr Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
title_full_unstemmed Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
title_sort Identification of Ligands for the Tau Exon 10 Splicing Regulatory Element RNA Using Dynamic Combinatorial Chemistry
dc.creator.none.fl_str_mv López-Senín, Paula
Gómez-Pinto, Irene
Grandas Sagarra, Anna
Marchán Sancho, Vicente
author López-Senín, Paula
author_facet López-Senín, Paula
Gómez-Pinto, Irene
Grandas Sagarra, Anna
Marchán Sancho, Vicente
author_role author
author2 Gómez-Pinto, Irene
Grandas Sagarra, Anna
Marchán Sancho, Vicente
author2_role author
author
author
dc.subject.none.fl_str_mv Química combinatòria
Bioquímica
RNA
Reconeixement molecular
Combinatorial chemistry
Biochemistry
RNA
Molecular recognition
topic Química combinatòria
Bioquímica
RNA
Reconeixement molecular
Combinatorial chemistry
Biochemistry
RNA
Molecular recognition
description We describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome 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 (EC(50)): 2-58 μM), 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.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/44407
url https://hdl.handle.net/2445/44407
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió preprint del document publicat a: http://dx.doi.org/10.1002/chem.201002065
Chemistry-A European Journal, 2011, vol. 17, num. 6, p. 1946-1953
http://dx.doi.org/10.1002/chem.201002065
dc.rights.none.fl_str_mv (c) Wiley-VCH, 2011
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Wiley-VCH, 2011
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417530282475520
score 15,301603

Similares en LA Referencia