title: Reversible Bioconjugation: Biodegradable Poly(phosphate)-Protein Conjugates.
abstract: Protein-polymer conjugates are widely used to improve the pharmacokinetic properties of therapeutic proteins. Commercially available conjugates employ poly(ethylene glycol) (PEG) as the protective polymer; however, PEG has a number of shortcomings, including non-biodegradability and immunogenicity, that call for the development of alternatives. Here, the synthesis of biodegradable poly(phosphate), that is, poly(ethyl ethylene phosphate) (PEEP), by organo-catalyzed anionic ring-opening polymerization exhibiting dispersity values Ð < 1.3 is reported. Polymers with molecular weights between 2000 and 33 200 g mol-1are then ω-functionalized with a succinimidyl carbonate group and subsequently conjugated to model proteins. These are the first conjugates based on polyphosphates which degraded upon exposure to phosphodiesterase. As is the case for PEGylated therapeutics, residual in vitro activity of the PPEylated conjugates depends on the extent of protein modification. These results suggest that PEEP exhibits the desired properties of a biopolymer for use in next generation, fully degradable drug delivery systems.
authors.affiliation: Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128, Mainz, Germany.|Graduate School Material Science in Mainz, Staudinger Weg 9, 55128, Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Steinbach
authors.affiliation: Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128, Mainz, Germany.|Graduate School Material Science in Mainz, Staudinger Weg 9, 55128, Mainz, Germany.
authors.forename: Greta
authors.initials: G
authors.lastname: Becker
authors.affiliation: Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Spiegel
authors.affiliation: CNR Istituto Officina dei Materiali c/o Institut Laue Langevin, 38000, Grenoble, France.
authors.forename: Tamiris
authors.initials: T
authors.lastname: Figueiredo
authors.affiliation: CNR Istituto Officina dei Materiali c/o Institut Laue Langevin, 38000, Grenoble, France.|Institut Lumière Matière, Université de Lyon 1, 69622, Lyon, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Russo
authors.affiliation: Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: Frederik R
authors.initials: FR
authors.lastname: Wurm
mesh_terms: D000818:Animals; D002254:Carbonates / Q000737:chemistry; D002374:Catalase / Q000737:chemistry*; D002417:Cattle; D004337:Drug Carriers; D006868:Hydrolysis; D008958:Models, Molecular; D008970:Molecular Weight; D043264:Phosphodiesterase I / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D011122:Polyphosphates / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013388:Succinimides / Q000737:chemistry
chemical_list: D002254:Carbonates; D004337:Drug Carriers; D011122:Polyphosphates; D013388:Succinimides; C085786:succinimidyl carbonate; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D002374:Catalase; D043264:Phosphodiesterase I
keywords: PEGylation; biodegradable polymer; poly(phosphoester)s; protein-polymer conjugates