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)
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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“Studies have demonstrated that proper glycosylation profiles can improve recombinant protein properties such as increase their stability and half-life in blood circulation and decrease their immunogenicity (Ashwell and Harford, 1982;Runkel et al., 1998;Ghaderi et al., 2010;Ghaderi et al., 2012;Jefferis, 2016a;Jefferis, 2016b;Kuriakose et al., 2016).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Runkel et al., 1998
Citations
Cites
Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis
Jacobs, L. D., Cookfair, D. L., Rudick, R. A., Herndon, R. M., Richert, J. R., Salazar, A. Μ., Fischer, J. S., Goodkin, D. E., Granger, C. V., Simon, J. H., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410390304 · Cited by 2,446
Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis
The IFNB Multiple Sclerosis Study Group (1993) · Neurology · doi:10.1212/wnl.43.4.655 · Cited by 2,085
Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis
Paty, D. W., Li, D. K. B., the UBC MS/MRI Study Group, & the IFNB Multiple Sclerosis Study Group (1993) · Neurology · doi:10.1212/wnl.43.4.662 · Cited by 1,964
Girard, M., Duquette, P., & Sibley, W. A. (1993) · Cited by 1,197
Stewart, W. E. (1979) · Springer eBooks · doi:10.1007/978-3-7091-3432-0 · Cited by 1,165
Rademacher, T. W., Parekh, R. B., & Dwek, R. A. (1988) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.57.070188.004033 · Cited by 1,144
Lis, H., & Sharon, N. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18347.x · Cited by 840
The interferon system. A bird's eye view of its biochemistry.
Sen, G. C., & Lengyel, P. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42719-6 · Cited by 633
Glycoproteins: what are the sugar chains for?
Paulson, J. C. (1989) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(89)90062-5 · Cited by 461
Influence of the Carbohydrate Moiety on the Stability of Glycoproteins
Wang, C., Eufemi, M., Turano, C., & GIARTOSIO, A. (1996) · Biochemistry · doi:10.1021/bi9517704 · Cited by 344
Gibson, R., Schlesinger, S., & Kornfeld, S. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50804-8 · Cited by 249
α and α Interferons and Their Receptor and Their Friends and Relations
Uzé, G., Lutfalla, G., & Mogensen, K. E. (1995) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1995.15.3 · Cited by 241
Dubé, S., Fisher, J. W., & Powell, J. S. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77865-x · Cited by 229
Zinc mediated dimer of human interferon-α2b revealed by X-ray crystallography
Radhakrishnan, R., Walter, L. J., Hruza, A. W., Reichert, P., Trotta, P. P., Nagabhushan, T. L., & Walter, M. R. (1996) · Structure · doi:10.1016/s0969-2126(96)00152-9 · Cited by 227
The interferons: Biological effects, mechanisms of action, and use in multiple sclerosis
Weinstock‐Guttman, B., Ransohoff, R. M., Kinkel, R. P., & Rudick, R. A. (1995) · Annals of Neurology · doi:10.1002/ana.410370105 · Cited by 225
The crystal structure of human interferon β at 2.2-Å resolution
Karpusas, M., Nolte, M. C., Benton, C. B., Meier, W., Lipscomb, W. N., & Goelz, S. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.22.11813 · Cited by 218
Self-citationSite-specific mutagenesis of the human fibroblast interferon gene.
Mark, D. F., Lu, S.-D., Creasey, A. A., Yamamoto, R., & Lin, L. S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5662 · Cited by 196
Davis, D., Liu, X., & Segaloff, D. L. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.2.7776966 · Cited by 195
Expression of human fibroblast interferon gene in Escherichia coli
Derynck, R., Remaut, E., Saman, E., Stanssens, P. E., Clercq, E. D., Content, J., & Fiers, W. (1980) · Nature · doi:10.1038/287193a0 · Cited by 192
Modulation of protein structure and function by asparagine-linked glycosylation
O'Connor, S. E., & Imperiali, B. (1996) · Chemistry & Biology · doi:10.1016/s1074-5521(96)90064-2 · Cited by 188
Jost, L. M., Kirkwood, J. M., & Whiteside, T. L. (1992) · Journal of Immunological Methods · doi:10.1016/s0022-1759(12)80003-2 · Cited by 182
Kagawa, Y., Takasaki, S., Utsumi, J., Hosoi, K., Shimizu, H., Kochibe, N., & Kobata, A. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77864-8 · Cited by 182
Interferon : principles and medical applications
Baron, S. (1992) · Medical Entomology and Zoology · Cited by 158
Actions of cytokines on the immune response and viral interactions: An overview
Peters, M. (1996) · Hepatology · doi:10.1002/hep.510230436 · Cited by 153
Ng, D., Hiebert, S. W., & Lamb, R. A. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.1989 · Cited by 119
Conradt, H. S., Egge, H., Peter‐Katalinić, J., Reiser, W., Siklosi, T., & Schaper, K. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47838-6 · Cited by 106
Mitsui, Y., Senda, T., Shimazu, T., Matsuda, S., & Utsumi, J. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90068-o · Cited by 71
Alam, J. J., Goelz, S. E., Rioux, P. P., Scaramucci, J., Jones, W. E., McAllister, A., Campion, M., & Rogge, M. C. (1997) · Pharmaceutical Research · doi:10.1023/a:1012128406432 · Cited by 57
Self-citationRefined Crystal Structure of Recombinant Murine Interferon-β at 2.15 Å Resolution
Senda, T., Saitoh, S., & Mitsui, Y. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0544 · Cited by 44
Interferons: Biochemistry and mechanisms of action
Tyring, S. K. (1995) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(95)90402-6 · Cited by 42
Wingfield, P. T., Graber, P., Turcatti, G., Movva, N. R., PELLETIER, M., Craig, S., Rose, K., & Miller, C. G. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb14610.x · Cited by 41
Folding, Unfolding, and Refolding of the Vesicular Stomatitis Virus Glycoprotein
Mathieu, M. E., Grigera, P. R., Helenius, A., & Wagner, R. R. (1996) · Biochemistry · doi:10.1021/bi952924i · Cited by 33
A homology model of human interferon α‐2
Murgolo, N., Windsor, W. T., Hruza, A. W., Reichert, P., Tsarbopoulos, A., Baldwin, S., Huang, E., Pramanik, B. N., Ealick, S. E., & Trotta, P. P. (1993) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340170109 · Cited by 23
Properties of Non-glycosylated Human Interferon-beta from MG63 Cells
Watanabe, Y., & Kawade, Y. (1983) · Journal of General Virology · doi:10.1099/0022-1317-64-6-1391 · Cited by 14
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Instability, stabilization, and formulation of liquid protein pharmaceuticals
Wang, W. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00152-0 · Cited by 1,094
Post-translational modifications in the context of therapeutic proteins
Walsh, G., & Jefferis, R. (2006) · Nature Biotechnology · doi:10.1038/nbt1252 · Cited by 1,007
Protein aggregation and its inhibition in biopharmaceutics
Wang, W. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.11.014 · Cited by 1,023
Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines, Goodin, D. S., Frohman, E. M., Garmany, G. P., Halper, J., Likosky, W., LUBLIN, F. D., Silberberg, D. H., Stuart, W. H., & van den Noort, S. (2002) · Neurology · doi:10.1212/wnl.58.2.169 · Cited by 797
Effects of glycosylation on the stability of protein pharmaceuticals
Solá, R. J., & Griebenow, K. H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21504 · Cited by 643
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
- Published
- 1998-04
- Volume
- 15
- Issue
- 4
- Pages
- 641-649
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- 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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