Anticoagulant heparan sulfate: structural specificity and biosynthesis |
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Authors: | Jian Liu Lars C Pedersen |
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Institution: | (1) Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Rm 309, Beard Hall, Chapel Hill, NC 27599, USA;(2) Laboratory of Structural Biology, the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA |
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Abstract: | 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. |
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Keywords: | Heparin Heparan sulfate Sulfotransferase Anticoagulant Oligosaccharide Herpes simplex virus |
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