Synthesis of stably glycosylated therapeutic glycoproteins

The majority of therapeutic drugs now in use are “so-called” small molecules – compounds that exert their desirable effect by interrupting or otherwise interfering with an abnormal physiological process. More recently, a new class of protein-based drugs has been developed, including various growth factors and Epoetin. Most protein-based drugs have sugars attached to their surface that are known as glycoproteins. These sugars play a role in directing the drug to its site of action and maintaining the protein in the bloodstream. If enzymes in a patient’s body cut or cleave the sugar molecules from the protein, the drug is cleared from the body. If scientists could produce more stable forms of glycoproteins, the drugs would remain in the bloodstream, reducing and potentially eliminating the need and costs of frequent doses. Using newly developed methodologies created in the laboratory of his supervisor Dr. Stephen Withers, Dr. Young-Wan Kim is working to address this issue by engineering new enzymes that would attach sugars via a sulfur atom and allow, for the first time, the generation of stable versions of these therapeutic proteins.