FIELD: biotechnology, gene engineering, medicine.
SUBSTANCE: new chimerical enzyme proteins, in particular proteins comprising fragments of porcine uricase and baboon uricase (PBC and PKS) are obtained by increasing of number of accessible PEG-binding sites in mammalian uricase by substitution of at least one fragment of mammalian lysine-free native enzyme amino acid sequence with homological lysine-containing uricase fragment of mammalian belonging to another specie and screening of uricase variants based on activity and immunogenicity after conjunction with PEG. Disclosed uricase variants maintain after PEGylation sufficiently the same uricolytic activity that non-modified enzyme and are sufficiently non-immunogenic ones. Also describes are methods for production of new chimerical uricase proteins by recombinant DNA technologies and vector constructs and expression systems used therefore.
EFFECT: intermediates for medicines with low immunogenicity and enhanced bioavalibility.
16 cl, 14 dwg, 4 tbl, 7 ex
Title |
Year |
Author |
Number |
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|
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