Engineered acid-stabile human interferon gamma.
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.
Kontsek
P
P
Institute of Virology, Slovak Academy of Sciences, Bratislava, 842 46, Slovakia. viruipeko@nic.savba.sk
Waschütza
G
G
Kontseková
E
E
Otto
B
B
D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004220:Disulfides; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D014644:Genetic Variation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D011994:Recombinant Proteins; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; D004220:Disulfides; D011994:Recombinant Proteins; D007371:Interferon-gamma