Recent Advances in Enzymes and Chemoenzymatic Synthesis of Tetrasaccharide Linkage Region of Proteoglycans

Proteoglycans (PGs) play roles in many important biological events, including growth factor signaling, wound repair, blood coagulation, brain development, and neural stem cell migration. As the glycosaminoglycan chain of PGs is attached to the core protein through a tetrasaccharide linkage region, it is important to decipher the intricate control of the multitude of enzymes engaged in biosynthesis of the linkage region. During the past two decades, significant advances have been achieved in our understanding of the identity and interactions of these enzymes as well as the control of their activities. Furthermore, the knowledge gained on biosynthesis of the linkage region has enabled the synthesis of structurally well‐defined proteoglycan‐associated glycopeptides. The expression, activity, and substrate profile of enzymes and the latest development of chemoenzymatic synthesis of linkage region‐bearing glycopeptides are summarized in this review.