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- W2198987390 abstract "Heparin has been used as an anticoagulant drug for more than 70 years. The global distribution of contaminated heparin in 2007, which resulted in adverse clinical effects and over 100 deaths, emphasizes the necessity for safer alternatives to animal-sourced heparin. The structural complexity and heterogeneity of animal-sourced heparin not only impedes safe access to these biologically active molecules, but also hinders investigations on the significance of structural constituents at a molecular level. Efficient methods for preparing new synthetic heparins with targeted biological activity are necessary not only to ensure clinical safety, but to optimize derivative design to minimize potential side effects. Low molecular weight heparins have become a reliable alternative to heparin, due to their predictable dosages, long half-lives, and reduced side effects. However, heparin oligosaccharide synthesis is a challenging endeavor due to the necessity for complex protecting group manipulation and stereoselective glycosidic linkage chemistry, which often result in lengthy synthetic routes and low yields. Recently, chemoenzymatic syntheses have produced targeted ultralow molecular weight heparins with high-efficiency, but continue to be restricted by the substrate specificities of enzymes. To address the need for access to homogeneous, complex glycosaminoglycan structures, we have synthesized novel heparan sulfate glycopolymers with well-defined carbohydrate structures and tunable chain length through ring-opening metathesis polymerization chemistry. These polymers recapitulate the key features of anticoagulant heparan sulfate by displaying the sulfation pattern responsible for heparin’s anticoagulant activity. The use of polymerization chemistry greatly simplifies the synthesis of complex glycosaminoglycan structures, providing a facile method to generate homogeneous macromolecules with tunable biological and chemical properties. Through the use of in vitro chromogenic substrate assays and ex vivo clotting assays, we found that the HS glycopolymers exhibited anticoagulant activity in a sulfation pattern and length-dependent manner. Compared to heparin standards, our short polymers did not display any activity. However, our longer polymers were able to incorporate in vitro and ex vivo characteristics of both low-molecular-weight heparin derivatives and heparin, displaying hybrid anticoagulant properties. These studies emphasize the significance of sulfation pattern specificity in specific carbohydrate-protein interactions, and demonstrate the effectiveness of multivalent molecules in recapitulating the activity of natural polysaccharides." @default.
- W2198987390 created "2016-06-24" @default.
- W2198987390 creator A5070413980 @default.
- W2198987390 date "2013-01-01" @default.
- W2198987390 modified "2023-09-27" @default.
- W2198987390 title "Synthesis and Biological Activity of Anticoagulant Heparan Sulfate Glycopolymers" @default.
- W2198987390 cites W122335598 @default.
- W2198987390 cites W1495482938 @default.
- W2198987390 cites W1500988371 @default.
- W2198987390 cites W1514571277 @default.
- W2198987390 cites W1533768632 @default.
- W2198987390 cites W1535367341 @default.
- W2198987390 cites W1581586115 @default.
- W2198987390 cites W158324379 @default.
- W2198987390 cites W1595277218 @default.
- W2198987390 cites W1608390571 @default.
- W2198987390 cites W1621500924 @default.
- W2198987390 cites W1628030746 @default.
- W2198987390 cites W1674650032 @default.
- W2198987390 cites W1766167996 @default.
- W2198987390 cites W176929667 @default.
- W2198987390 cites W1786317249 @default.
- W2198987390 cites W1814046987 @default.
- W2198987390 cites W1820870565 @default.
- W2198987390 cites W1891400877 @default.
- W2198987390 cites W1913314522 @default.
- W2198987390 cites W1933438817 @default.
- W2198987390 cites W1950519844 @default.
- W2198987390 cites W1964080848 @default.
- W2198987390 cites W1965078663 @default.
- W2198987390 cites W1965650017 @default.
- W2198987390 cites W1965748825 @default.
- W2198987390 cites W1965986284 @default.
- W2198987390 cites W1966296230 @default.
- W2198987390 cites W1966752841 @default.
- W2198987390 cites W1967051574 @default.
- W2198987390 cites W1968321554 @default.
- W2198987390 cites W1969487877 @default.
- W2198987390 cites W1970322877 @default.
- W2198987390 cites W1971540677 @default.
- W2198987390 cites W1972126468 @default.
- W2198987390 cites W1972161933 @default.
- W2198987390 cites W1973233314 @default.
- W2198987390 cites W1973653019 @default.
- W2198987390 cites W1974863339 @default.
- W2198987390 cites W1976173820 @default.
- W2198987390 cites W1976894600 @default.
- W2198987390 cites W1977223059 @default.
- W2198987390 cites W1977321526 @default.
- W2198987390 cites W1978456175 @default.
- W2198987390 cites W1980567615 @default.
- W2198987390 cites W1981004224 @default.
- W2198987390 cites W1981430544 @default.
- W2198987390 cites W1982393004 @default.
- W2198987390 cites W1983532547 @default.
- W2198987390 cites W1984402172 @default.
- W2198987390 cites W1985919028 @default.
- W2198987390 cites W1987702283 @default.
- W2198987390 cites W1987792040 @default.
- W2198987390 cites W1989196923 @default.
- W2198987390 cites W1989683953 @default.
- W2198987390 cites W1989989356 @default.
- W2198987390 cites W1992034958 @default.
- W2198987390 cites W1992884184 @default.
- W2198987390 cites W1993605313 @default.
- W2198987390 cites W1993707501 @default.
- W2198987390 cites W1993745855 @default.
- W2198987390 cites W1994533814 @default.
- W2198987390 cites W1994974479 @default.
- W2198987390 cites W1995064954 @default.
- W2198987390 cites W1998428201 @default.
- W2198987390 cites W1998717980 @default.
- W2198987390 cites W1998924915 @default.
- W2198987390 cites W2000742521 @default.
- W2198987390 cites W2001027118 @default.
- W2198987390 cites W2004010183 @default.
- W2198987390 cites W2004746423 @default.
- W2198987390 cites W2005921248 @default.
- W2198987390 cites W2005960069 @default.
- W2198987390 cites W2006406220 @default.
- W2198987390 cites W2007486148 @default.
- W2198987390 cites W2007530420 @default.
- W2198987390 cites W2008009936 @default.
- W2198987390 cites W2008581828 @default.
- W2198987390 cites W2009148595 @default.
- W2198987390 cites W2009441924 @default.
- W2198987390 cites W2009929707 @default.
- W2198987390 cites W2010493770 @default.
- W2198987390 cites W2012481284 @default.
- W2198987390 cites W2013021801 @default.
- W2198987390 cites W2016269821 @default.
- W2198987390 cites W2020316252 @default.
- W2198987390 cites W2023689609 @default.
- W2198987390 cites W2024291269 @default.
- W2198987390 cites W2024600640 @default.
- W2198987390 cites W2025653570 @default.
- W2198987390 cites W2026186036 @default.
- W2198987390 cites W2028307231 @default.
- W2198987390 cites W2028756560 @default.
- W2198987390 cites W2029454917 @default.