title: Biological Functions of Interferon β-1a Are Enhanced By Deamidation.
abstract: Human type I Interferons (IFN-β, IFN-ɛ, IFN-κ, IFN-ω, and 12 subtypes of IFN-α) are a family of pleiotropic cytokines with antiviral, antiproliferative, and immunomodulatory activities. They signal through the same cell surface receptors, IFNAR1 and IFNAR2, yet evoking markedly differential potency. One differentiating factor of IFN-β from other type I interferons is the presence of a consensus sequence (NG) for deamidation. Comparing almost completely deamidated IFN-β-1a with untreated IFN-β-1a, this present study reports the increased activities in 3 in-vitro bioassays testing the antiviral, antiproliferative, and immunomodulatory properties, respectively, of the molecule. Deamidated IFN-β-1a has the potential to improve current therapies in multiple sclerosis, and its ability to potentiate the MHC-Class I expression suggests a clinical benefit in diseases where the downmodulation of the MHC-class I expression plays a role (eg, in immuno-oncology combination therapies or antiviral agents). The present study on IFN-β deamidation adds a new prospective on deamidation as part of a posttranslational modification code that allows the modulation of the biological properties of proteins. Moreover, it underlines the unique IFN-β-1a properties that differentiate this molecule from other members of the type I interferon family.
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Renato
authors.initials: R
authors.lastname: Mastrangeli
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Luisa
authors.initials: L
authors.lastname: Iozzino
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Ludovica
authors.initials: L
authors.lastname: Lanzoni
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Gabriella
authors.initials: G
authors.lastname: Angiuoni
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Cristian
authors.initials: C
authors.lastname: Ferrao
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Anna
authors.initials: A
authors.lastname: Izzo
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fiumi
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Fabio
authors.initials: F
authors.lastname: Camerini
authors.affiliation: 1 Analytical Development Biotech Products, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Michele
authors.initials: M
authors.lastname: Mascia
authors.affiliation: 2 Biotech Development Program, Merck Biopharma, an affiliate of Merck KgaA , Darmstadt, Germany, Aubonne, Switzerland .
authors.forename: Wolf
authors.initials: W
authors.lastname: Palinsky
authors.affiliation: 3 Biotech Development Program, CMC Sciences & Intelligence, Merck Serono SpA, an affiliate of Merck KgaA , Darmstadt, Germany, Rome, Italy .
authors.forename: Horst
authors.initials: H
authors.lastname: Bierau
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D002942:Circular Dichroism; D003412:Cricetulus; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000068556:Interferon beta-1a / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D007155:Immunologic Factors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D000068556:Interferon beta-1a