Anticoagulant heparan sulfate: structural specificity and biosynthesis.
Heparan sulfate (HS) is present on the surface of endothelial and surrounding tissues in large quantities. It plays important roles in regulating numerous functions of the blood vessel wall, including blood coagulation, inflammation response, and cell differentiation. HS is a highly sulfated polysaccharide containing glucosamine and glucuronic/iduronic acid repeating disaccharide units. The unique sulfated saccharide sequences of HS determine its specific functions. Heparin, an analog of HS, is the most commonly used anticoagulant drug. Because of its wide range of biological functions, HS has become an interesting molecule to biochemists, medicinal chemists, and developmental biologists. In this review, we summarize recent progress toward understanding the interaction between HS and blood-coagulating factors, the biosynthesis of anticoagulant HS and the mechanism of action of HS biosynthetic enzymes. Furthermore, knowledge of the biosynthesis of HS facilitates the development of novel enzymatic approaches to synthesize HS from bacterial capsular polysaccharides and to produce polysaccharide end products with high specificity for the biological target. These advancements provide the foundation for the development of polysaccharide-based therapeutic agents.
Liu
Jian
J
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Rm 309, Beard Hall, Chapel Hill, NC 27599, USA. jian_liu@unc.edu
Pedersen
Lars C
LC
D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism; D001709:Biotechnology / Q000379:methods; D002236:Carbohydrate Conformation; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D018139:Simplexvirus / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D000925:Anticoagulants; D006497:Heparan Sulfate; D011135:Polysaccharides, Bacterial; D015238:Sulfotransferases