Hyaluronic acid (HA), is a linear, high molecular weight (up to 2 x 104 kDa) glycosaminoglycan assembled from β-1,3-linked-2-acetamido-2-deoxy-D-glucose-β-(1→4)-D-glucuronic acid repeating units. As an extracellular matrix component, HA is involved in a wide variety of biological processes, such as cell migration, proliferation, adhesion, recognition, tumor invasion and tumor inhibition. Degradation of HA during inflammation and tumor growth results in the accumulation of fragments of HA (sHA). These fragments are potent activators of angiogenesis, dendritic cells and the expression of matrix metalloproteases by tumors.
sHA is commonly prepared by partial enzymatic degradation of HA followed by fractionation using size exclusion chromatography. Only a small amount of heterogeneous and contaminated mixtures of sHA are often isolated by this method. However, the size of sHA is critical for its biological activity, so we develop a scalable synthesis starting from glucosamine hydrochloride and 1,2;4,6-diisopropylglucofuranose for the production of defined lengths of sHA (scheme 1).
Scheme 1. Hyaluronic acid fragments and the starting materials.