dc.contributor.author | Jiménez Trujillo, Tania | |
dc.contributor.author | Botero Hincapié, Juliana Andrea | |
dc.contributor.author | Otaegui Ansa, Dorleta | |
dc.contributor.author | Calvo, Javier | |
dc.contributor.author | Hernandez, Frank J. | |
dc.contributor.author | San Sebastián Larzabal, Eider ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.date.accessioned | 2021-10-21T08:53:42Z | |
dc.date.available | 2021-10-21T08:53:42Z | |
dc.date.issued | 2021-09-09 | |
dc.identifier.citation | Journal Of Medicinal Chemistry 64(17) : 12855-12864 (2021) | es_ES |
dc.identifier.issn | 0022-2623 | |
dc.identifier.issn | 1520-4804 | |
dc.identifier.uri | http://hdl.handle.net/10810/53506 | |
dc.description.abstract | An undecamer oligonucleotide probe based on a pair of deoxythymidines flanked by several modified nucleotides is a specific and highly efficient biosensor for micrococcal nuclease (MNase), an endonuclease produced by Staphylococcus aureus. Herein, the interaction mode and cleavage process on such oligonucleotide probes are identified and described for the first time. Also, we designed truncated pentamer probes as the minimum-length substrates required for specific and efficient biosensing. By means of computational (virtual docking) and experimental (ultra-performance liquid chromatography-mass spectrometry and matrix-assisted laser desorption ionization time-of-flight) techniques, we perform a sequence/structure-activity relationship analysis, propose a catalytically active substrate-enzyme complex, and elucidate a novel two-step phosphodiester bond hydrolysis mechanism, identifying the cleavage sites and detecting and quantifying the resulting probe fragments. Our results unravel a picture of both the enzyme-biosensor complex and a two-step cleavage/biosensing mechanism, key to the rational oligonucleotide design process. | es_ES |
dc.description.sponsorship | F.J.H. acknowledges the support from the Wallenberg Centre for Molecular Medicine (WCMM) Linkoping, Sweden, and The Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linkoping University (Faculty grant SFO-Mat-LiU no. 2009-00971). T.J. acknowledges the support from the program Torres Quevedo (MINECO-grant number PTQ-17-09382), and J.B. acknowledges the support from the industrial doctorate program (MINECO-grant number DI-16-08891). E.S.S. acknowledges SGIker (UPV/EHU/ERDF/EF) for the generous allocation of computational resources. J.C. and D.O. acknowledge the support from the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency.grant no. MDM-2017-0720 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Chemical Society | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/MDM-2017-0720 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/DI-16-08891 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/PTQ-17-09382 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | staphylococcal nuclease | es_ES |
dc.subject | infection | es_ES |
dc.subject | docking | es_ES |
dc.subject | complex | es_ES |
dc.subject | glide | es_ES |
dc.title | Rational Design and Experimental Analysis of Short-Oligonucleotide Substrate Specificity for Targeting Bacterial Nucleases | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://pubs-acs-org.ehu.idm.oclc.org/doi/10.1021/acs.jmedchem.1c00884# | es_ES |
dc.identifier.doi | 10.1021/acs.jmedchem.1c00884 | |
dc.departamentoes | Ciencia y tecnología de polímeros | es_ES |
dc.departamentoes | Química aplicada | es_ES |
dc.departamentoeu | Kimika aplikatua | es_ES |
dc.departamentoeu | Polimeroen zientzia eta teknologia | es_ES |