Chemical, enzymatic and biological synthesis of hyaluronic acids

Hyaluronic acid (HA) is a major glycosaminoglycan, a family of structurally complex, linear, anionic hetero-co-polysaccharides. HA is important in various anatomical structures including the eyes, joints, heart and myriad intricate tissues, and is currently widely used in the therapeutics and cosmetics areas. The synthesis of HA of well-defined and uniform chain lengths is of major interest for the development of safer and more reliable drugs and to gain a better understanding of its structure-activity relationships. However, HA has received less attention from the synthetic carbohydrate community compared with other members of the glycosaminoglycan family. In this review, we examine the remarkable progress that has been made in the chemical and chemoenzymatic synthesis of HA, providing a broad spectrum of options to access HA of well controlled chain lengths.