Abstract
Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticoagulants / antagonists & inhibitors*
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Anticoagulants / chemical synthesis*
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Anticoagulants / pharmacology
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Antithrombins / metabolism
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Antithrombins / pharmacology
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Carbohydrate Sequence
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Cell Adhesion Molecules, Neuronal / metabolism
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Chromatography, High Pressure Liquid
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Factor Xa Inhibitors
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Hemorrhage / drug therapy
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Heparin, Low-Molecular-Weight / antagonists & inhibitors*
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Heparin, Low-Molecular-Weight / chemical synthesis*
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Heparin, Low-Molecular-Weight / pharmacology
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Humans
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Indicators and Reagents
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Isotope Labeling
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Protamines / pharmacology
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Spectrometry, Mass, Electrospray Ionization
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Sulfur Radioisotopes
Substances
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Anticoagulants
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Antithrombins
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Cell Adhesion Molecules, Neuronal
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Factor Xa Inhibitors
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Heparin, Low-Molecular-Weight
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Indicators and Reagents
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Protamines
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Stab2 protein, mouse
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Sulfur Radioisotopes