ArticleProceedings of the National Academy of Sciences of the United States of America2003
Rational design of low-molecular weight heparins with improved in vivo activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
The trial behind it
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
24 citing papers in PubMed, 89 citations in OpenAlex.
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- A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding.Heliyon · 2024Article
- A review of advanced hydrogels for cartilage tissue engineering.Frontiers in bioengineering and biotechnology · 2024Review
- Investigation of the pharmacokinetic properties of synthetic heparan sulfate oligosaccharides.Glycobiology · 2023Article
- Synthesis of 3-Biochemistry · 2020Article
- Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins.Science translational medicine · 2017Article
- Injectable hydrogels for cartilage and bone tissue engineering.Bone research · 2017Review
- Polysaccharide-based nanoparticles for theranostic nanomedicine.Advanced drug delivery reviews · 2016Review
- Discovery of a heparan sulfate 3-O-sulfation specific peeling reaction.Analytical chemistry · 2015Article
- Capillary electrophoretic analysis of isolated sulfated polysaccharides to characterize pharmaceutical products.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine.Progress in polymer science · 2014Article
- Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis.Experimental and therapeutic medicine · 2014Article
- Homogeneous low-molecular-weight heparins with reversible anticoagulant activity.Nature chemical biology · 2014Article
- Scientific considerations in the review and approval of generic enoxaparin in the United States.Nature biotechnology · 2013Article
- Directing the biological activities of heparan sulfate oligosaccharides using a chemoenzymatic approach.Glycobiology · 2012Article
- Glycomics analysis of mammalian heparan sulfates modified by the human extracellular sulfatase HSulf2.PloS one · 2011Article
- Comparative glycomics using a tetraplex stable-isotope coded tag.Analytical chemistry · 2010Article
- Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.The journal of Tehran Heart Center · 2010Article
- M118, a novel low-molecular weight heparin with decreased polydispersity leads to enhanced anticoagulant activity and thrombotic occlusion in ApoE knockout mice.Journal of thrombosis and thrombolysis · 2009Article
- A rationally designed heparin, M118, has anticoagulant activity similar to unfractionated heparin and different from Lovenox in a cell-based model of thrombin generation.Journal of thrombosis and thrombolysis · 2009Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Heparin and low-molecular weight heparins (LMWHs), complex, sulfated polysaccharides isolated from endogenous sources, are potent modulators of hemostasis. Heparin and LMWHs interact with multiple components of the coagulation cascade to inhibit the clotting process. Pharmaceutical preparations of these complex polysaccharides, typically isolated from porcine intestinal mucosa, are heterogeneous in length and composition and, hence, highly polydisperse. Because of the structural heterogeneity of heparin and LMWHs, correlating their activity with a particular structure or structural motif has been a challenging task. Herein, we demonstrate a practical analytical method that enables the measurement of a structural correlate to in vivo anticoagulant function. With this understanding we have developed LMWHs with increased anticoagulant activity and decreased polydispersity. In addition to the pronounced anti-Xa and anti-IIa activity of these LMWHs, we also demonstrate that they possess desirable in vivo pharmacokinetic properties, the ability to cause the release of tissue factor pathway inhibitor (TFPI) from the endothelium, complete bioavailability through s.c. delivery, and the ability to inhibit both venous and arterial thromboses. Importantly, from a clinical safety point of view, unlike LMWHs presently used in the clinic, we show that these LMWHs are rapidly and completely neutralized by protamine. Together, the findings presented herein demonstrate a facile approach for the creation of designer LMWHs with optimal activity profiles.
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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.