Fig. 2. Chemoenzymatic scheme for the synthesis of ULMW and LMW heparins. Panel A shows the structures of disaccharide repeating units of HS. The biosynthesis of HS is completed through four sulfotransferases and one C5-epimerase. The action site for each sulfotransferase and the C5-epimerase is indicated. Panel B shows the synthetic steps for the synthesis of anticoagulant 6-mer, 8-mer and 12-mer products. These oligosaccharides have unique properties as a synthetic heparin candidate. The synthesis started from monosaccharide 1-O-(p-nitrophenyl) glucuronide (GlcA-pNP), which is commercially available. The recovery yield at each synthetic step is indicated below the reaction arrow. Abbreviations: NST, N-sulfotransferase; PAPS, 3′-phosphoadenosine 5′-phosphosulfate; PmHS2, heparosan synthase 2 from Pasteurella multocida.
