title: Noncovalent PEGylation of L-asparaginase using PEGylated polyelectrolyte.
abstract: Noncovalent PEGylation has great potential for stabilization of therapeutic proteins. Here, we demonstrated that the noncovalent PEGylation with a PEGylated polyelectrolyte stabilized a therapeutic protein, l-asparaginase (ASNase). Anionic ASNase and cationic poly(ethylene glycol)-block-poly(N,N-dimethylaminoethyl methacrylate) (PEG-b-PAMA) formed a water-soluble protein-polyelectrolyte complex (PPC) without loss of secondary structure and enzyme activity. PPC with PEG-b-PAMA successfully inhibited the shaking-induced inactivation and aggregation of ASNase as well as protease digestion, corresponding to the behaviors of covalently PEGylated ASNase. Thus, noncovalent PEGylation by PEGylated polyelectrolytes is a new candidate for handling of therapeutic proteins.
authors.affiliation: Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kurinomaru
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D001215:Asparaginase / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011109:Polymethacrylic Acids; C539837:poly(acrylic acid-co-methacrylic acid); D011092:Polyethylene Glycols; D001215:Asparaginase
keywords: complexation; pegylation; polyelectrolytes; protein aggregation; protein formulation; stabilization