Complex Natural Product Heparin: Biosynthesis, Biology, and Application via Synthetic Heparins

Abstract

Heparin is a natural product consisting of a mixture of structurally complex polysaccharides that is isolated from porcine intestine, bovine lung, and bovine intestine. Rich in negative charges, heparin interacts with proteins, affecting numerous biological processes. It is biosynthesized by a group of specialized enzymes, including glycosyl transferases, carbohydrate-epimerase, and sulfotransferases. As a medicinally important natural product, heparin is a widely used anticoagulant drug during surgical procedures and as prophylaxis agent for patients with high risk of deep vein thrombosis. The structural heterogeneity in heparin complicates processes for the quality control and regulatory efforts to ensure the purity and safety of heparin drug. A chemoenzymatic approach has been developed to prepare synthetic heparin, mimicking the biosynthesis of heparin in vivo. The synthetic heparin can be synthesized in a highly purified form under regulated manufacture facility, eliminating the concerns associated with the animal-sourced heparin. In addition, synthetic heparin displays superior pharmacological effects to animal-sourced heparin, suitable for patients with special needs. This chapter summarizes the current understandings of the biology and biosynthesis of heparin as well as efforts toward the development of synthetic heparin.