PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity

Autor: Elizaveta A. Zvonova, I. V. Goldenkova-Pavlova, Maksim B. Degterev, Andrei V. Petrov, Alexander Yu. Vishnevsky, Marina A. Sudomoina, Alexander V. Ershov, Grigoriy N. Poroshin, Andrey P. Karpov, A.V. Eremeev, Olga A. Ershova, Alexander M. Shuster, Sergey V. Ruchko
Rok vydání: 2016
Předmět:
Zdroj: Applied Microbiology and Biotechnology. 101:1975-1987
ISSN: 1432-0614
0175-7598
DOI: 10.1007/s00253-016-7944-3
Popis: Recombinant interferon-β1b (IFN-β1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation. To solve this problem, we constructed two variants of PASylated IFN-β1b, with PAS sequence at C- or N-terminus of IFN-β1b. The PAS-modified proteins demonstrated 4-fold increase in hydrodynamic volume of the molecule combined with 2-fold increase of in vitro biological activity, as well as advanced stability and solubility of the protein in solution as opposed to unmodified IFN-β1b. Our results demonstrate that PASylation has a positive impact on stability, solubility, and functional activity of IFN-β1b and potentially might improve pharmacokinetic properties of the molecule as a therapeutic agent.
Databáze: OpenAIRE
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