PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity
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- 作者：Elizaveta A. Zvonova ; Alexander V. Ershov…
- 关键词：Interferon ; β1b ; PASylation ; Expression ; Solubility ; Stability ; Biological activity
- 刊名：Applied Microbiology and Biotechnology
- 出版年：2017
- 出版时间：March 2017
- 年：2017
- 卷：101
- 期：5
- 页码：1975-1987
- 全文大小：
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Microbiology; Microbial Genetics and Genomics; Biotechnology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1432-0614
- 卷排序：101
文摘
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.