ArticleProceedings of the National Academy of Sciences of the United States of America2000
Cleavage of the antithrombin III binding site in heparin by heparinases and its implication in the generation of low molecular weight heparin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 130 citations in OpenAlex.
- Spatial Profiling of Glycosaminoglycans (GAGomics) From Laser Microdissected Mouse Brain.Molecular & cellular proteomics : MCP · 2026Article
- Recent analytical advances in the detection and characterization of 3-O-sulfated heparan sulfate.Analytical and bioanalytical chemistry · 2025Review
- Expanding the Role of Heparin Derivatives in Oncology: From Anticoagulation to Antitumor Activity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery.Organic letters · 2024Article
- Influence of saccharide modifications on heparin lyase III substrate specificities.Glycobiology · 2022Article
- Heparinase Digestion of 3-Frontiers in medicine · 2022Article
- Heparin and Its Derivatives: Challenges and Advances in Therapeutic Biomolecules.International journal of molecular sciences · 2021Review
- A rechargeable anti-thrombotic coating for blood-contacting devices.Biomaterials · 2021Article
- The 3-Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Identification of Protein Recognition Elements within Heparin Chains Using Enzymatic Foot-Printing in Solution and Online SEC/MS.Analytical chemistry · 2020Article
- Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches.BMC genomics · 2020Article
- Structural Analysis of Heparin-Derived 3-O-Sulfated Tetrasaccharides: Antithrombin Binding Site Variants.Journal of pharmaceutical sciences · 2017Article
- Parenteral administration of factor Xa/IIa inhibitors limits experimental aortic aneurysm and atherosclerosis.Scientific reports · 2017Article
- An integrated approach using orthogonal analytical techniques to characterize heparan sulfate structure.Glycoconjugate journal · 2017Article
- New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Analysis of 3-O-sulfo group-containing heparin tetrasaccharides in heparin by liquid chromatography-mass spectrometry.Analytical biochemistry · 2014Article
- Article
- Heparan sulfate 3-O-sulfation: a rare modification in search of a function.Matrix biology : journal of the International Society for Matrix Biology · 2014Review
- Structural features of glycol-split low-molecular-weight heparins and their heparin lyase generated fragments.Analytical and bioanalytical chemistry · 2014Article
- Heparin dodecasaccharide containing two antithrombin-binding pentasaccharides: structural features and biological properties.The Journal of biological chemistry · 2013Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
Heparin has been used as a clinical anticoagulant for more than 50 years, making it one of the most effective pharmacological agents known. Much of heparin's activity can be traced to its ability to bind antithrombin III (AT-III). Low molecular weight heparin (LMWH), derived from heparin by its controlled breakdown, maintains much of the antithrombotic activity of heparin without many of the serious side effects. The clinical significance of LMWH has highlighted the need to understand and develop chemical or enzymatic means to generate it. The primary enzymatic tools used for the production of LMWH are the heparinases from Flavobacterium heparinum, specifically heparinases I and II. Using pentasaccharide and hexasaccharide model compounds, we show that heparinases I and II, but not heparinase III, cleave the AT-III binding site, leaving only a partially intact site. Furthermore, we show herein that glucosamine 3-O sulfation at the reducing end of a glycosidic linkage imparts resistance to heparinase I, II, and III cleavage. Finally, we examine the biological and pharmacological consequences of a heparin oligosaccharide that contains only a partial AT-III binding site. We show that such an oligosaccharide lacks some of the functional attributes of heparin- and heparan sulfate-like glycosaminoglycans containing an intact AT-III site.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.