Approaches to the synthesis of heparin.
The biosynthesis of heparin is initiated by formation of [GlcA-GlcNAc]n polysaccharide chains linked to the core protein of a proteoglycan structure. The polymer is transformed into the mature polysaccharide by a series of modification reactions which involve N-deacetylation and N-sulfation of GlcNAc units, C5 epimerization of GlcA to IdoA residues, and O-sulfation at different positions. Incomplete modification, controlled in part by the substrate specificities of the corresponding enzymes, provides the complex saccharide sequences that are typical for heparin and, in particular, for heparan sulfate. One such structure is the antithrombin-binding region which is comprised by a specific pentasaccharide sequence with a 3-O-sulfated GlcN marker group. Aspects of regulation of polymer modification are discussed.
Lindahl
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Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala.
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D002240:Carbohydrate Sequence; D006493:Heparin / Q000096:biosynthesis* / Q000138:chemical synthesis; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000138:chemical synthesis; D008407:Mast Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure
D000991:Antithrombins; D006493:Heparin; D006497:Heparan Sulfate