{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T02:39:35Z","timestamp":1788230375859,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008049","name":"Fundaci\u00f3n Banco Santander","doi-asserted-by":"publisher","award":["XSAN192006"],"award-info":[{"award-number":["XSAN192006"]}],"id":[{"id":"10.13039\/100008049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad Europea de Madrid","award":["2020\/UEM42"],"award-info":[{"award-number":["2020\/UEM42"]}]},{"name":"Spanish Ministry of Economia y Competitividad","award":["BIO2017-89754-C2-"],"award-info":[{"award-number":["BIO2017-89754-C2-"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["SGR17\/861"],"award-info":[{"award-number":["SGR17\/861"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Herein we report the first proof for the application of type II 2\u2032-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\u2032-deoxy-5-fluorouridine (dFUrd), 2\u2032-deoxy-2-fluoroadenosine (dFAdo), and 2\u2032-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\u2032-deoxyribosyltransferases (NDTs) in cancer treatment.<\/jats:p>","DOI":"10.3390\/biom11010120","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T04:55:31Z","timestamp":1611032131000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular Basis of NDT-Mediated Activation of Nucleoside-Based Prodrugs and Application in Suicide Gene Therapy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-2523","authenticated-orcid":false,"given":"Javier","family":"Acosta","sequence":"first","affiliation":[{"name":"Applied Biotechnology Group, European University of Madrid, c\/ Tajo s\/n, Villaviciosa de Od\u00f3n, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Applied Biotechnology Group, European University of Madrid, c\/ Tajo s\/n, Villaviciosa de Od\u00f3n, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"S\u00e1nchez-Murcia","sequence":"additional","affiliation":[{"name":"Division of Physiological Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6\/III, A-8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Fillat","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-8306","authenticated-orcid":false,"given":"Jes\u00fas","family":"Fern\u00e1ndez-Lucas","sequence":"additional","affiliation":[{"name":"Division of Physiological Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6\/III, A-8010 Graz, Austria"},{"name":"Grupo de Investigaci\u00f3n en Ciencias Naturales y Exactas, GICNEX, Universidad de la Costa, CUC, Calle 58 # 55-66 Barranquilla, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021, January 14). 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