title: Site-Specific Polymer Conjugation Stabilizes Therapeutic Enzymes in the Gastrointestinal Tract.
abstract: The site-specific conjugation of polymers to multiple engineered cysteine residues of a prolyl endopeptidase leads to its stabilization in the gastrointestinal tract of rats, without compromising the activity relative to the native enzyme. The importance of polymer attachment sites is investigated, as well as the significance of polymer structure.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Schulz
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Patt
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Basler
authors.affiliation: Department of Chemistry and Applied Biosciences, Laboratory of Organic Chemistry, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Hajo
authors.initials: H
authors.lastname: Kries
authors.affiliation: Department of Chemistry and Applied Biosciences, Laboratory of Organic Chemistry, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
authors.affiliation: EMT Research Center, Institut National de la Recherche Scientifique (INRS), J3X 1S2 Varennes, Quebec, Canada.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Gauthier
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), 8093, Zurich, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism* / Q000627:therapeutic use; D004795:Enzyme Stability; D041981:Gastrointestinal Tract / Q000378:metabolism*; D008958:Models, Molecular; D016941:Myxococcus xanthus / Q000201:enzymology; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats
chemical_list: D011092:Polyethylene Glycols; D010450:Endopeptidases
keywords: gastrointestinal stability; poly(ethylene glycol); site-specific polymer conjugation, therapeutic enzymes