title: Arginine-specific modification of proteins with polyethylene glycol.
abstract: In this study, the residue-selective modification of proteins with polymers at arginine residues is reported. The difficulty in modifying arginine residues lies in the fact that they are less reactive than lysine residues. Consequently, typical chemo-selective reactions which employ "kinetic" selectivity (active esters, Michael addition, etc.) cannot be used to target these residues. The chemistry exploited herein relies on "thermodynamic" selectivity to achieve selective modification of arginine residues. ω-Methoxy poly(ethylene glycol) bearing an α-oxo-aldehyde group was synthesized and used to demonstrate the selective modification of lysozyme at arginine residues. In addition, the optimization of reaction conditions for coupling as well as the stability of the formed adduct toward dilution, toward a nucleophilic buffer, and toward acidification are reported. It was concluded that this approach is a convenient, mild, selective, and catalyst-free method for protein modification.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut des Matériaux and Institut des Sciences et Ingénierie Chimiques, Lausanne, Switzerland.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Gauthier
authors.forename: Harm-Anton
authors.initials: HA
authors.lastname: Klok
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D001120:Arginine / Q000737:chemistry*; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D011092:Polyethylene Glycols; D001120:Arginine; D009113:Muramidase