Chemical Biology of Glycoproteins
CHAPTER 13: Selective Chemical Glycosylation of Therapeutic Proteins
Published:20 Mar 2017
Special Collection: 2017 ebook collectionSeries: Chemical Biology
Qun Zhou, 2017. "Selective Chemical Glycosylation of Therapeutic Proteins", Chemical Biology of Glycoproteins, Zhongping Tan, Lai-Xi Wang
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Carbohydrate is one of the major macromolecules in nature. Glycosylation (covalent attachment of carbohydrate) occurs in macromolecules, including nucleic acids, proteins and lipids. Glycans play important roles in many biological processes, such as inflammation, immune reactions, and intracellular transport. To improve understanding of these essential roles, many therapeutic proteins have been in vitro glycosylated to improve their pharmacokinetics and pharmacodynamics. The conjugation of hydrophilic polymers, including polyethylene glycol or polysaccharides, to native glycans or amino acid residues in the protein often resulted in increased serum half-life, reduced immunogenicity or enhanced stability. Glycan modification using either enzymatic or chemical conjugation methods also facilitated protein targeting to disease-affected tissues. In addition, the glycans from the well-conserved glycosylation site at Asn-297 in a monoclonal antibody provide the sites for selective conjugation of either anticancer drugs or diagnostic agents. Taken together, selective chemical glycosylation has been applied as a unique approach in generation of protein therapeutics with an improved therapeutic index for multiple diseases. Some glycosylated proteins are being used in patient treatment or are under clinical investigation.