title: Modification with polysialic acid-PEG copolymer as a new method for improving the therapeutic efficacy of proteins.
abstract: A 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.
authors.affiliation: a Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Biotechnology , Jiangnan University , Wuxi , China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Biotechnology , Jiangnan University , Wuxi , China.
authors.forename: Shaozeng
authors.initials: S
authors.lastname: Lu
authors.affiliation: a Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Biotechnology , Jiangnan University , Wuxi , China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: a Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Biotechnology , Jiangnan University , Wuxi , China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: a Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Biotechnology , Jiangnan University , Wuxi , China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Zhan
mesh_terms: D000818:Animals; D002175:Candida / Q000201:enzymology*; D004795:Enzyme Stability; D005260:Female; D007700:Kinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012794:Sialic Acids / Q000737:chemistry*; D014503:Urate Oxidase / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D012794:Sialic Acids; C021319:polysialic acid; D011092:Polyethylene Glycols; D014503:Urate Oxidase
keywords: Block copolymer; immunogenicity; polyethylene glycol; polysialic acid; uricase