Glycan-targeted PEGylation for selective modification of proteins

Abstract

Protein therapeutic agents frequently have short half-life in circulation due to their filtration by kidney, the action of proteolytic enzymes, the recognition by the immune system or the generation of neutralizing antibodies. To overcome these short comings, covalent modification with polyethylene glycol (PEG) has been widely applied. Among the numerous techniques developed for the introduction of the PEG chain, PEGylation at the carbohydrate moiety has the advantage of being site-selective, generating functional proteins with increased bioavailability. In this chapter we discuss different methodologies and applications of glycan-PEGylation, including glycoPEGylation and PEGylation of native glycoproteins, in particular coagulation factors used for treatment of hemophilia that are currently in the market or in the clinical trial phase