Reagents for the Covalent Attachment of mPEG to Peptides and Proteins

Abstract

In the last forty years, the conjugation of methoxy-poly(ethylene glycol) (mPEG) has evolved to become a well-established technology for the improvement of the physicochemical and therapeutic properties of biopharmaceutical peptides and proteins (PEGylation). In fact, eleven PEGylated products are available nowadays in the marketplace, while several others are under clinical evaluation. Ubiquitously present nucleophillic groups, such as the terminal -NH2 group, the ε-NH2 group of lysine and the -SH group of cysteine, have all been used to couple peptides and proteins to mPEG derivatives. Moreover, site-selective, reversible and enzymatic PEGylation have recently gained increasing attention among the biopharmaceutical community. Th e aim of this chapter is to summarize the most relevant and recent achievements obtained in the PEGylation of peptides and proteins, with an emphasis on the chemistry underlying the currently available methods for the preparation of mPEG reagents, as well as the chemistry involved in the PEGylation reactions.