Site Directed Disulfide PEGylation of Interferon-β-1b with Fork Peptide Linker
| Autor: | Gholam Hossein Riazi, Jamshid Davoodi, Loghman Firoozpour, Mohammad Taheri, Shayan Abbasi, Sama Pirkalkhoran, Homa Farahani, Hossein Lanjanian, Shahriar Pooyan |
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| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Models Molecular Protein Conformation alpha-Helical Chemistry Organic Chemistry technology industry and agriculture Biomedical Engineering Disulfide bond Pharmaceutical Science Bioengineering Peptide macromolecular substances Bioavailability Polyethylene Glycols Interferon β 1b Protein structure PEG ratio Biophysics PEGylation Disulfides Peptides Linker Biotechnology Interferon beta-1b |
| Zdroj: | Bioconjugate chemistry. 31(3) |
| ISSN: | 1520-4812 |
| Popis: | The attachment of PEG to biopharmaceuticals has been applied for enhancement of bioavailability and improved stability. The PEG polymer is highly hydrated; thus effective attachment to inaccessible sites could be hindered. We have devised a scheme to address this issue by introducing a considerable distance between PEG and protein by addition of a linear peptide, appended to long chained reactive linkers. Second, the position of PEG conjugation directly affects biological activity. Accordingly, a disulfide bond could be considered as an ideal choice for site directed PEGylation; but reactivity of both thiol moieties to bridging reagent is critical for maintenance of protein structure. In our design, a forked structure with two arms provides essential flexibility to account for dissociation of reduced cysteines. An efficient yield for disulfide PEGylation of IFN-β1b was attained and specificity, biophysical characterization, biological activity, and pharmacokinetics were surveyed. |
| Databáze: | OpenAIRE |
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