Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
Heparin is a highly sulfated polysaccharide that is commercially available for anticoagulation. As an animal sourced product, heparin is heterogeneous and contains polysaccharides that differ in length and sulfation patterns. In 2007, heparin sourced from porcine intestines was contaminated with over-sulfated chondroitan sulfate. Taken in conjunction with other possible pharmacological activities, there have been efforts to synthesize distinct heparan sulfate polysaccharides in a cost-effective manner, including chemoenzymatic synthesis. Some of the limitations associated with chemoenzymatic synthesis include expensive starting materials and incomplete synthesis leading to a product mixture. In an effort to overcome the first obstacle we developed two methods to efficiently synthesize the starting materials for heparan sulfate chemoenzymatic synthesis, including UDP-GlcNTFA and UDP-GlcA, from glucosamine and glucose respectively. To overcome the second obstacle, we explored possible inhibition by the chemoenzymatic co-factor PAPS. Both of these projects aim to advance the production of heparin and heparan sulfate polysaccharides.