2016
DOI: 10.1007/s00253-016-7944-3
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PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity

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 increas… Show more

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Cited by 32 publications
(27 citation statements)
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“…Due to the limited periplasmic space, the expression level of PASylated Fab′ was not very significant within this space, while the amount of secreted PASylated Fab′ within the culture medium was approximately 50 times higher than that of the periplasmic space, which may be explained by the increased size of the expressed protein. This finding was supported by the previous studies indicating the effect of prolonged cultivation conditions and high cell density of the culture in leakage of E. coli proteins into the culture medium and can be an interesting economical issue in industrial production of such pharmaceutics in E. coli in order to enhance the yield of active protein extraction and purification 25 27 .…”
Section: Discussionsupporting
confidence: 81%
See 1 more Smart Citation
“…Due to the limited periplasmic space, the expression level of PASylated Fab′ was not very significant within this space, while the amount of secreted PASylated Fab′ within the culture medium was approximately 50 times higher than that of the periplasmic space, which may be explained by the increased size of the expressed protein. This finding was supported by the previous studies indicating the effect of prolonged cultivation conditions and high cell density of the culture in leakage of E. coli proteins into the culture medium and can be an interesting economical issue in industrial production of such pharmaceutics in E. coli in order to enhance the yield of active protein extraction and purification 25 27 .…”
Section: Discussionsupporting
confidence: 81%
“…An exact molecular weight of 82,312.2 Da was measured for PASylated Fab′ using mass spectroscopy, while its electrophoretic mobility was around 200 kDa on SDS-PAGE. This discrepancy has been reported by previous studies indicating the role of hydrophilic amino acids such as alanine, proline, and serine in decreasing SDS-binding properties and mobility of PASylated protein on SDS-PAGE 18 , 19 , 25 .…”
Section: Discussioncontrasting
confidence: 81%
“…Indeed, several PASylated biopharmaceuticals have been generated up to now, for example growth hormone,9 leptin,10 antibody fragments,9, 11 interferons,9, 12, 13 erythropoietin,14 a complement inhibitor,15 and interleukin‐1 receptor antagonist (IL‐1Ra). All these PASylated proteins have demonstrated beneficial properties:8 (i) high solubility and stability, (ii) full biofunctionality both in vitro and in animal models, (iii) high bioavailability when injected subcutaneously, intraperitoneally or intramuscularly and (iv) drastically prolonged plasma half‐life—by one to two orders of magnitude—depending on the length of the PAS chain (typically, 600 residues).…”
Section: Introductionmentioning
confidence: 99%
“…Despite being administered at an overall 16-fold lower dosage than IFNβ alone, PAS-YNSα8 outperformed the control group in an experimental autoimmune encephalomyelitis model, as indicated by a decrease in infiltrating macrophages in the central nervous system and an increase in regulatory T cells [ 429 ]. In a separate study by Zvonona et al, PAS was fused to the C-terminus of IFN-β1b and resulted in a 4-fold increase in hydrodynamic radius compared to free IFN-β1b [ 430 ]. The fusion protein also notably increased IC50 2-fold compared to free IFN-β1b, an accomplishment considering PEGylation of the same interferon decreases its activity.…”
Section: Applications In Drug Deliverymentioning
confidence: 99%