The University of New Mexico

Seminar:

Developing a chemoenzymatic approach to prepare carbohydrate-based medicines

January 20, 2017

Jian Liu

Heparin is a hihly sulfate polysaccharide that is widely used as a anticoagulant drug in hospitals. The supply of heparin is currently relying on the isolation from porcine intestines through a long and poorly regulated supply chain.  Developing a cost-effective method to prepare synthetic heparin under pharamaceutical grade manufacture facility will improve the safety of heparin drug.  However, synthesis of heparin a using a purely chemical approach remains to be challenging.  A chemoenzymatic method has been recently developed to prepare synthetic heparin.  The methods only involves the use of five different enzymes, including sulfotransferases, an epimerase and glycosyltransferases.  Using these enzymes, a highly diverse heparan sulfate oligosaccharide library have been prepared.  In addition, this method has been successfully utilized to synthesize ultra-low molecular weight heparin and low-molecular weight heparins, to improve the pharmacology of heparin-based anticoauglant drugs.  The enzyme-based synthetic approach has synthesized more than 50 oligosaccharides with different sulfation patterns and size.  The availability of hepain-like oligosaccharide library offers a unique tool to study the function and activity relationship of heparin in biological systems.