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A trivalent TNF-R2 as a new tumor necrosis factor alpha-blocking molecule.
Contreras, María A; Macaya, Luis; Manrique, Viana; Camacho, Frank; González, Alain; Montesinos, Raquel; Toledo, Jorge R; Sánchez, Oliberto.
Afiliação
  • Contreras MA; Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
  • Macaya L; Center for Biotechnology and Biomedicine Spa, Concepción, Chile.
  • Manrique V; Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
  • Camacho F; Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
  • González A; Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
  • Montesinos R; Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
  • Toledo JR; Faculty of Basic Sciences, University of Medellin, Medellin, Colombia.
  • Sánchez O; Biotechnology and Biopharmaceutical Laboratory, Pathophysiology Department, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
Proteins ; 89(11): 1557-1564, 2021 11.
Article em En | MEDLINE | ID: mdl-34250652
ABSTRACT
The 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colágeno / Fator de Necrose Tumoral alfa / Receptores Tipo II do Fator de Necrose Tumoral / Endotoxinas / Etanercepte / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colágeno / Fator de Necrose Tumoral alfa / Receptores Tipo II do Fator de Necrose Tumoral / Endotoxinas / Etanercepte / Anti-Inflamatórios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article