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A trivalent TNF-R2 as a new tumor necrosis factor alpha-blocking molecule

dc.contributor.authorContreras M.A
dc.contributor.authorMacaya L
dc.contributor.authorManrique V
dc.contributor.authorCamacho F
dc.contributor.authorGonzález A
dc.contributor.authorMontesinos R
dc.contributor.authorToledo J.R
dc.contributor.authorSánchez O.
dc.date.accessioned2022-09-14T14:33:26Z
dc.date.available2022-09-14T14:33:26Z
dc.date.created2021
dc.identifier.issn8873585
dc.identifier.urihttp://hdl.handle.net/11407/7369
dc.descriptionThe neutralization of tumor necrosis factor alpha (TNFα) with biopharmaceuticals is a successful therapy for inflammatory diseases. Currently, one of the main TNFα-antagonists is Etanercept, a dimeric TNF-R2 ectodomain. Considering that TNFα and its receptors are homotrimers, we proposed that a trimeric TNF-R2 ectodomain could be an innovative TNFα-antagonist. Here, the 3cTNFR2 protein was designed by the fusion of the TNF-R2 ectodomain with the collagen XV trimerization domain. 3cTNFR2 was produced in HEK293 cells and purified by immobilized metal affinity chromatography. Monomers, dimers, and trimers of 3cTNFR2 were detected. The interaction 3cTNFR2-TNFα was assessed. By microscale thermophoresis, the KD value for the interaction was 4.17 ± 0.88 nM, and complexes with different molecular weights were detected by size exclusion chromatography-high performance liquid chromatography. Moreover, 3cTNFR2 neutralized the TNFα-induced cytotoxicity totally in vitro. Although more studies are required to evaluate the anti-inflammatory effect, the results suggest that 3cTNFR2 could be a TNFα-antagonist agent. © 2021 Wiley Periodicals LLC.eng
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85110256301&doi=10.1002%2fprot.26177&partnerID=40&md5=1d0e08e4dd8daefb08022099917d3757
dc.sourceProteins: Structure, Function and Bioinformatics
dc.titleA trivalent TNF-R2 as a new tumor necrosis factor alpha-blocking molecule
dc.typeArticle
dc.rights.accessrightsinfo:eu-repo/semantics/restrictedAccess
dc.publisher.programCiencias Básicas
dc.type.spaArtículo
dc.identifier.doi10.1002/prot.26177
dc.subject.keywordProtein engineeringeng
dc.subject.keywordProtein–protein interactioneng
dc.subject.keywordTumor necrosis factor alphaeng
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationContreras, M.A., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile, Center for Biotechnology and Biomedicine Spa, Concepción, Chile
dc.affiliationMacaya, L., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile
dc.affiliationManrique, V., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile
dc.affiliationCamacho, F., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile
dc.affiliationGonzález, A., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile, Faculty of Basic Sciences, University of Medellin, Medellin, Colombia
dc.affiliationMontesinos, R., Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile
dc.affiliationToledo, J.R., Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile
dc.affiliationSánchez, O., Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile, Center for Biotechnology and Biomedicine Spa, Concepción, Chile
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dc.type.coarhttp://purl.org/coar/resource_type/c_6501
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.type.driverinfo:eu-repo/semantics/article
dc.identifier.reponamereponame:Repositorio Institucional Universidad de Medellín
dc.identifier.repourlrepourl:https://repository.udem.edu.co/
dc.identifier.instnameinstname:Universidad de Medellín


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