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Glycoengineering of interferon-? 1a improves its biophysical and pharmacokinetic properties.


ABSTRACT: The purpose of this study was to develop a biobetter version of recombinant human interferon-? 1a (rhIFN-? 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-? 1a via site-directed mutagenesis. Glycoengineering of rhIFN-? 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-? mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-? 1a. Glycoengineering had no effect on rhIFN-? ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-? could be a biobetter version of rhIFN-? 1a with a potential for use as a drug against multiple sclerosis.

SUBMITTER: Song K 

PROVIDER: S-EPMC4032242 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glyco  ...[more]

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