Cysteine-pegylated proteins

Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or... – Modification of viruses

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435188, 435212, 435219, C12N 1500, C12N 996, C12N 948, C12N 950

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active

057668973

ABSTRACT:
Methods and compositions are provided for the production of PEGylated proteins having polyethylene glycol covalently bound to a cysteine residue present in either the naturally-occurring protein or introduced by site-specific mutation. Where the cysteine residue is introduced by mutation, the site for mutation is selected on the basis of the presence of an N-linked glycosylation site or the position of the residue which is normally solvent-accessible in the naturally-occurring protein. The modified proteins produced by the method of the invention are referred to as cysteine-PEGylated proteins. Proteins PEGylated according to the invention have increased half-lives following administration to a subject and decreased immunogenicity and antigenicity, while retaining substantially the same level of biological activity as that of the naturally-occurring, unmodified protein. Modification of proteins according to methods of the invention thus provide improved pharmaceutical compositions.

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