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Cited by 304interferon and immune responsesMultiple Sclerosis Research StudiesGlycosylation and Glycoproteins Research

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Structural and Functional Differences Between Glycosylated and Non-glycosylated Forms of Human Interferon-β (IFN-β)

Runkel, Laura, Meier, Werner, Pepinsky, R. Blake, Karpusas, Michael, Whitty, Adrian, Kimball, Kathleen, Brickelmaier, Margot, Muldowney, Celine, Jones, Wendy, Goelz, Susan E.·1998·Pharmaceutical Research
DOI 10.1023/a:1011974512425
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Abstract

Purpose Two recombinant IFN-beta products have been approved for the treatment of multiple sclerosis, a glycosylated form with the predicted natural amino acid sequence (IFN-beta-1a) and a non-glycosylated form that has a Met-1 deletion and a Cys-17 to Ser mutation (IFN-beta-1b). The structural basis for activity differences between IFN-beta-1a and IFN-beta-1b, is determined. Methods In vitro antiviral, antiproliferative and immunomodulatory assays were used to directly compare the two IFN-beta products. Size exclusion chromatography (SEC), SDS-PAGE, thermal denaturation, and X-ray crystallography were used to examine structural differences. Results IFN-beta-1a was 10 times more active than IFN-beta-1b with specific activities in a standard antiviral assay of 20 x 10(7) IU/mg for IFN-beta-1a and 2 x 10(7) IU/mg for IFN-beta-1b. Of the known structural differences between IFN-beta-1a and IFN-beta-1b, only glycosylation affected in vitro activity. Deglycosylation of IFN-beta-1a produced a decrease in total activity that was primarily caused by the formation of an insoluble disulfide-linked IFN precipitate. Deglycosylation also resulted in an increased sensitivity to thermal denaturation. SEC data for IFN-beta-1b revealed large, soluble aggregates that had reduced antiviral activity (approximated at 0.7 x 10(7) IU/mg). Crystallographic data for IFN-beta-1a revealed that the glycan formed H-bonds with the peptide backbone and shielded an uncharged surface from solvent exposure. C…

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Metadata

Authors
Runkel, L., Meier, W., Pepinsky, R. B., Karpusas, M., Whitty, A., Kimball, K., Brickelmaier, M., Muldowney, C., Jones, W., & Goelz, S. E.
Affiliations
Biogen (United States) (US)
Corresponding author
Runkel, Laura
ORCID
Whitty, Adrian
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
1998-04
Volume
15
Issue
4
Pages
641-649
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1011974512425
OpenAlex
W329292291
Cited by
304
References
34
Citations by year
2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 16 · 2015: 10 · 2014: 16 · 2013: 16 · 2012: 13
FWCI
3.46
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmaceutical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
interferon-beta, glycosylation, recombinant interferon, multiple sclerosis, antiviral activity, protein stability, thermal denaturation, protein aggregation, disulfide bonds, protein structure
MeSH terms
Interferon beta-1a, Interferon beta-1b, Adjuvants, Immunologic, Antiviral Agents, Base Sequence, Cell Division, Cell Line, Cysteine, Encephalomyocarditis virus, Glycosylation, Humans, Major Histocompatibility Complex, Molecular Sequence Data, Mutation, Recombinant Proteins, Serine, Interferon-beta, Cardiovirus Infections

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