Abstract
ABSTRACTA new protein derivatization method was developed with a block copolymer to reduce the immunogenicity of therapeutic proteins. The block copolymer consisted of polyethylene glycol (PEG) and polysialic acid (PSA), a nonimmunogenic and biodegradable biopolymer. Uricase was used as a model protein. Molecular weight analysis results indicated that the uricase–PEG–PSA conjugate was linked with 2.5 copolymers for each uricase unit. The residual enzyme activity of the uricase with modification by the PEG–PSA copolymer was 72.4%. The tolerance and stability to heat, acid, alkaline, and trypsin treatments significantly improved compared with the native uricase. The immunogenicity of uricase modified with PEG–PSA copolymer was remarkably reduced. The transmission electron microscopy results of the uricase–PEG–PSA conjugate showed a spherical hydrated shell with a larger particle size. These findings proved that the PSA–PEG–protein conjugate is a formulation that can potentially be used to deliver the protein and peptide-based drugs.
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