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PubMed · 10843749

Engineered acid-stabile human interferon gamma.

P Kontsek·G Waschütza·E Kontseková·B Otto
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Abstract

Loss of anti-viral potency upon pH2-treatment is an inherent feature of interferon (IFN)-gamma. The phenomenon seems to be caused by dissociation of IFN-gamma homodimer into subunits upon acidification and subsequent self-association of monomers into aggregates with reduced activity after neutralization. We demonstrated that acid-stability could be engineered into human IFN-gamma without affecting its specific activity. An artificial intra-monomer disulphide bond E7C/S69C stabilizes the dimeric form of the cytokine, which retained its full bioactivity after exposure to pH2. Acidification did not modify the antigenic structure of IFN-gamma as proved by a panel of mouse anti-human IFNgamma antibodies.

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Amino Acid SubstitutionAnimalsAntiviral AgentsCell LineDisulfidesDrug StabilityEnzyme-Linked Immunosorbent AssayGenetic VariationHumansHydrogen-Ion ConcentrationInterferon-gammaMiceRecombinant ProteinsVesicular stomatitis Indiana virusJournal ArticleResearch Support, Non-U.S. Gov't

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P Kontsek, G Waschütza, E Kontseková, B Otto. 2000. Engineered acid-stabile human interferon gamma.. https://doi.org/10.1006/cyto.1999.0630

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