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Sequencing analysis and identification of the primary peptide component of the dialyzable leukocyte extract "Transferon Oral": The starting point to understand its mechanism of action

dc.creatorVallejo-Castillo, Luises_ES
dc.creatorFavari, Lilianaes_ES
dc.creatorVázquez-Leyva, Saides_ES
dc.creatorMellano-Sánchez, Gabrielaes_ES
dc.creatorMacías-Palacios, Zairaes_ES
dc.creatorLópez-Juárez, Leonardo E.es_ES
dc.creatorValencia-Flores, Luises_ES
dc.creatorMedina-Rivero, Emilioes_ES
dc.creatorChacón-Salinas, Rommeles_ES
dc.creatorPavón, Lenines_ES
dc.creatorPérez-Tapia, Sonia Mayraes_ES
dc.date2020
dc.date.accessioned2023-05-25T19:25:58Z
dc.date.available2023-05-25T19:25:58Z
dc.date.issued2020
dc.identifierJC08NC22es_ES
dc.identifier.urihttp://repositorio.inprf.gob.mx/handle/123456789/7696
dc.identifier.urihttps://doi.org/10.3389/fphar.2020.569039
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577238/
dc.descriptionTransferon Oral" is a peptide-derived product with immunomodulatory properties obtained from the lysis and dialysis of human buffy coat. Its active pharmaceutical ingredient, generically known as Dialyzable Leucocyte Extract, is a mixture of peptide populations with reproducible proportions among batches. "Transferon Oral" modulates IFN-γ, TNF-α, and IL-6 and increases the survival rate in a herpes infection murine model when oropharyngeally (ORO) administered, which correlate with clinical observations where "Transferon Oral" is used as a therapeutic auxiliary in inflammatory diseases. Notwithstanding, how a peptide-derived product elicits systemic modulation of cytokines when ORO administered remains unclear. To shed light on the pharmacology of "Transferon Oral" its peptide components must be known. Ten "Transferon Oral" batches were sequenced by mass spectrometry and the intact peptides were identified. The most abundant peptides were the monomeric human Ubiquitin (Ub), a globular low-molecular mass protein, and an Ub variant which lacks the two-terminal Gly (Ub-GG). Recombinant Ub prevented murine death when ORO administered in a herpes infection murine model. Besides, the percentage of survival increased in groups treated with Transferon Oral+Ub and decreased in groups treated with Ub-depleted "Transferon Oral" respect to the group treated with "Transferon Oral" only. Our findings indicate that the biological properties of "Transferon Oral" are partially associated to the Ub content. They suggest that Ub may activate its extracellular receptor (CXCR-4) in the stomach eliciting systemic immunomodulatory effects via vagus nerve. This is the first report that identifies an active component of "Transferon Oral" with the potential for the development of oral peptide immunomodulators.es_ES
dc.formatPDFes_ES
dc.language.isoenges_ES
dc.publisherFrontiers Mediaes_ES
dc.relation11:569039
dc.rightsAcceso Cerradoes_ES
dc.titleSequencing analysis and identification of the primary peptide component of the dialyzable leukocyte extract "Transferon Oral": The starting point to understand its mechanism of actiones_ES
dc.typeArtículoes_ES
dc.contributor.affiliationUnidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, México
dc.contributor.emaillkuriaki@imp.edu.mx (Lenin Pavón) mayra.perez@udibi.com.mx (Sonia Mayra Pérez-Tapia)
dc.relation.jnabreviadoFRONT PHARMACOL
dc.relation.journalFrontiers in Pharmacology
dc.identifier.placeSuiza
dc.date.published2020
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñiz
dc.identifier.doi10.3389/fphar.2020.569039
dc.subject.kwMS sequencing
dc.subject.kwTransferon
dc.subject.kwHuman dialyzable leukocyte extracts
dc.subject.kwImmunomodulatory drugs
dc.subject.kwMonomeric ubiquitin
dc.subject.kwOral peptides


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