RT Journal Article
T1 Molecular basis of NDT-mediated activation of nucleoside-based prodrugs and application in suicide gene therapy
A1 Acosta, Javier
A1 Pérez, Elena
A1 Sánchez Murcia, Pedro A.
A1 Fillat, Cristina
A1 Fernández Lucas, Jesús
AB Herein 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.
PB MDPI
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/109083
UL https://hdl.handle.net/20.500.14352/109083
LA eng
NO Acosta J, Pérez E, Sánchez-Murcia PA, Fillat C, Fernández-Lucas J. Molecular Basis of NDT-Mediated Activation of Nucleoside-Based Prodrugs and Application in Suicide Gene Therapy. Biomolecules 2021;11:120. https://doi.org/10.3390/biom11010120.
NO Ministerio de Economía y Competitividad (España)
NO Generalitat de Catalunya
NO Universidad Europea de Madrid
NO Fundación Santander
DS Docta Complutense
RD 8 abr 2025