Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins

摘要: Therapeutic proteins have revolutionized the treatment of many diseases but low activity or rapid clearance limits their utility. New approaches been taken to design drugs with enhanced in vivo and half-life reduce injection frequency, increase convenience, improve patient compliance. One recently used approach is glycoengineering, changing protein-associated carbohydrate alter pharmacokinetic properties proteins. This technology has applied erythropoietin resulted discovery darbepoetin alfa (DA), a hyperglycosylated analogue that contains two additional N-linked carbohydrates, threefold serum increased compared recombinant human (rHuEPO). The allows for less frequent dosing maintain target hemoglobin levels anemic patients. Carbohydrates on DA other molecules can also molecular stability, solubility, biological activity, immunogenicity. These are discussed.