Heparin, a highly sulfated polysaccharide anticoagulant, commands worldwide market of ~$7B.  Currently, heparin and related low molecular weight heparins (LMWHs, such as enoxaparin, tinzaparin, dalteparin), require an extraction from pig intestine.  In an effort to improve the sustainable manufacture of these critical, life-saving drugs our laboratory has undertaken the preparation of bioengineered heparin and chemoenzymatically synthesized LMWHs and ultra-LMWHs. These biotechnological processes should also allow the preparation of this critical drug under cGMP affording improved products and preventing the introduction of impurities, such as prions and viruses, and contaminants or adulterants, such as those responsible for the 2008 heparin contamination crisis. Novel LMWHs can also be prepared with improved pharmacological properties (i.e., defined pharmacokinetics, liver clearance and protamine reversibility) using chemoenzymatic synthesis. Our approach relies on chemical synthesis and transformations utilizing biosynthetic enzymes, including heparosan synthases, sulfotransferases and epimerase.  Chemoenzymatic synthesis is reliable over a wide range of scales and should be useful in both research and pharmaceutical applications.

Sustainable heparin-based therapeutics: CARB perspective

248th National Meeting (2014)

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