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Appl Microbiol Biotechnol. 2017 Mar;101(5):1975-1987. doi: 10.1007/s00253-016-7944-3. Epub 2016 Nov 10.

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

Author information

1
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia. berkovich@ibcgenerium.ru.
2
Generium Pharmaceutical, Testovskaya st. 10, ent. 2, Moscow, 123317, Russia.
3
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
4
Cellthera Pharm, Vladimirskaya street 14B, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
5
Institute of Plant Physiology, Russian Academy of Sciences, ul. Botanicheskaya 35, Moscow, 127276, Russia.
6
Inbio ventures, Testovskaya st. 10, ent. 2, Moscow, 123317, Russia.

Abstract

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.

KEYWORDS:

Biological activity; Expression; Interferon-β1b; PASylation; Solubility; Stability

PMID:
27833991
DOI:
10.1007/s00253-016-7944-3
[Indexed for MEDLINE]

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