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dc.creatorAcosta, Javier
dc.creatorPérez, Elena
dc.creatorSánchez-Murcia, Pedro A
dc.creatorFillat, Cristina
dc.creatorFernández-Lucas, Jesús
dc.date.accessioned2021-02-26T20:07:44Z
dc.date.available2021-02-26T20:07:44Z
dc.date.issued2021
dc.identifier.issn2218-273X
dc.identifier.urihttps://hdl.handle.net/11323/7937
dc.description.abstractHerein we report the first proof for the application of type II 2′-deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) in suicide gene therapy for cancer treatment. To this end, we first confirm the hydrolytic ability of LdNDT over the nucleoside-based prodrugs 2′-deoxy-5-fluorouridine (dFUrd), 2′-deoxy-2-fluoroadenosine (dFAdo), and 2′-deoxy-6-methylpurine riboside (d6MetPRib). Such activity was significantly increased (up to 30-fold) in the presence of an acceptor nucleobase. To shed light on the strong nucleobase dependence for enzymatic activity, different molecular dynamics simulations were carried out. Finally, as a proof of concept, we tested the LdNDT/dFAdo system in human cervical cancer (HeLa) cells. Interestingly, LdNDT/dFAdo showed a pronounced reduction in cellular viability with inhibitory concentrations in the low micromolar range. These results open up future opportunities for the clinical implementation of nucleoside 2′-deoxyribosyltransferases (NDTs) in cancer treatment.spa
dc.format.mimetypeapplication/pdfspa
dc.language.isoengspa
dc.publisherCorporación Universidad de la Costaspa
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.sourceBiomoleculesspa
dc.subjectChemotherapyspa
dc.subjectSuicide gene therapyspa
dc.subjectNucleoside analoguesspa
dc.subject2′-deoxyribosyltransferasespa
dc.subjectStructural bioinformaticsspa
dc.subjectMolecular dynamicsspa
dc.titleMolecular basis of Ndt-mediated activation of nucleoside-based prodrugs and application in suicide gene therapyspa
dc.typearticlespa
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dc.source.urlhttps://www.mdpi.com/2218-273X/11/1/120spa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.identifier.doihttps://doi.org/10.3390/biom11010120
dc.type.hasversioninfo:eu-repo/semantics/publishedVersionspa


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