Chemoenzymatic synthesis of classical and non-classical anticoagulant heparan sulfate polysaccharides.
Heparan sulfate (HS) polysaccharides interact with numerous proteins at the cell surface and orchestrate many different biological functions. Though many functions of HS are well established, only a few specific structures can be attributed to HS functions. The extreme diversity of HS makes chemical synthesis of specific bioactive HS structures a cumbersome and tedious undertaking that requires laborious and careful functional group manipulations. Now that many of the enzymes involved in HS biosynthesis are characterized, we show in this study how one can rapidly and easily assemble bioactive HS structures with a set of cloned enzymes. We have demonstrated the feasibility of this new approach to rapidly assemble antithrombin III-binding classical and non-classical anticoagulant polysaccharide structures for the first time.
D000990:Antithrombin III / Q000737:chemistry; D016367:Baculoviridae / Q000378:metabolism; D001671:Biochemistry / Q000379:methods; D002238:Carbohydrate Epimerases / Q000138:chemical synthesis* / Q000737:chemistry; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D015951:Factor Xa / Q000737:chemistry; D019763:Heparin Lyase / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011133:Polysaccharide-Lyases / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D015238:Sulfotransferases / Q000737:chemistry
D000990:Antithrombin III; D002238:Carbohydrate Epimerases; D015951:Factor Xa; D019763:Heparin Lyase; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D011134:Polysaccharides; D011994:Recombinant Proteins; D015238:Sulfotransferases; C021349:heparitinsulfate lyase; C430881:heparin-heparan sulfate-glucuronic acid C5-epimerase