Mostrar el registro sencillo del ítem

dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorOndono, Raul
dc.contributor.authorLirio, Ángel
dc.contributor.authorCarlos, Elvira
dc.contributor.authorÁlvarez-Marimon, Elena
dc.contributor.authorProvenzano, Claudia
dc.contributor.authorCardinali, Beatrice
dc.contributor.authorPérez-Alonso, Manuel
dc.contributor.authorPerálvarez-Marín, Alex
dc.contributor.authorBorrell Bilbao, José Ignacio
dc.contributor.authorFalcone, Germana
dc.contributor.authorEstrada Tejedor, Roger
dc.date.accessioned2024-05-24T18:10:04Z
dc.date.available2024-05-24T18:10:04Z
dc.date.issued2020-11-28
dc.identifier.issn2001-0370ca
dc.identifier.urihttp://hdl.handle.net/20.500.14342/4085
dc.description.abstractMyotonic Dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by toxic DMPK transcripts that carry CUG repeat expansions in the 3′ untranslated region (3′UTR). The intrinsic complexity and lack of crystallographic data makes noncoding RNA regions challenging targets to study in the field of drug discovery. In DM1, toxic transcripts tend to stall in the nuclei forming complex inclusion bodies called foci and sequester many essential alternative splicing factors such as Muscleblind-like 1 (MBNL1). Most DM1 phenotypic features stem from the reduced availability of free MBNL1 and therefore many therapeutic efforts are focused on recovering its normal activity. For that purpose, herein we present pyrido[2,3-d]pyrimidin-7-(8H)-ones, a privileged scaffold showing remarkable biological activity against many targets involved in human disorders including cancer and viral diseases. Their combination with a flexible linker meets the requirements to stabilise DM1 toxic transcripts, and therefore, enabling the release of MBNL1. Therefore, a set of novel pyrido[2,3-d]pyrimidin-7-(8H)-ones derivatives (1a-e) were obtained using click chemistry. 1a exerted over 20% MBNL1 recovery on DM1 toxic RNA activity in primary cell biology studies using patient-derived myoblasts. 1a promising anti DM1 activity may lead to subsequent generations of ligands, highlighting a new affordable treatment against DM1.ca
dc.format.extent11 p.ca
dc.language.isoengca
dc.publisherElsevierca
dc.relation.ispartofComputational and Structural Biotechnology Journalca
dc.rights© L'autor/aca
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalca
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.otherMyotonic dystrophyca
dc.subject.otherMolecular modellingca
dc.subject.otherRNA targetingca
dc.subject.otherSmall moleculeca
dc.subject.otherBase recognitionca
dc.subject.otherMiotonia atròficaca
dc.titleDesign of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1ca
dc.typeinfo:eu-repo/semantics/articleca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.subject.udc616.6ca
dc.subject.udc616.8ca
dc.identifier.doihttps://doi.org/10.1016/j.csbj.2020.11.053ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i ISCIII i FEDER/PN I+D/FIS13-0386ca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca


Ficheros en el ítem

 

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

© L'autor/a
Excepto si se señala otra cosa, la licencia del ítem se describe como http://creativecommons.org/licenses/by-nc-nd/4.0/
Compartir en TwitterCompartir en LinkedinCompartir en FacebookCompartir en TelegramCompartir en WhatsappImprimir