ArticleBiochemical and biophysical research communications2011
Identification of the site of binding of sulfated, low molecular weight lignins on thrombin.
Article in Biochemical and biophysical research communications, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Lignin-Based Mucus-Mimicking Antiviral Hydrogels with Enzyme Stability and Tunable Porosity.ACS applied materials & interfaces · 2025Article
- Designing Smaller, Synthetic, Functional Mimetics of Sulfated Glycosaminoglycans as Allosteric Modulators of Coagulation Factors.Journal of medicinal chemistry · 2023Review
- Lignosulfonic Acid Sodium Is a Noncompetitive Inhibitor of Human Factor XIa.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies.Current medicinal chemistry · 2020Review
- Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding site of thrombin.Thrombosis research · 2018Article
- A small group of sulfated benzofurans induces steady-state submaximal inhibition of thrombin.Bioorganic & medicinal chemistry letters · 2018Article
- Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.Scientific reports · 2016Article
- Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.Medicinal research reviews · 2014Review
- Substantial non-electrostatic forces are needed to induce allosteric disruption of thrombin's active site through exosite 2.Biochemical and biophysical research communications · 2014Article
- Targeting the GPIbα binding site of thrombin to simultaneously induce dual anticoagulant and antiplatelet effects.Journal of medicinal chemistry · 2014Article
- Designing allosteric regulators of thrombin. Exosite 2 features multiple subsites that can be targeted by sulfated small molecules for inducing inhibition.Journal of medicinal chemistry · 2013Article
- Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site.Journal of medicinal chemistry · 2013Article
- Sulfated pentagalloylglucoside is a potent, allosteric, and selective inhibitor of factor XIa.Journal of medicinal chemistry · 2013Article
- Designing allosteric regulators of thrombin. Monosulfated benzofuran dimers selectively interact with Arg173 of exosite 2 to induce inhibition.Journal of medicinal chemistry · 2012Article
- Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases.Biochemical and biophysical research communications · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sulfated, low molecular weight lignins (LMWLs), designed recently as macromolecular mimetics of the low molecular weight heparins (LMWHs), were found to exhibit a novel allosteric mechanism of inhibition of human thrombin, factor Xa and plasmin, which translates into potent human blood anticoagulation potential. To identify the site of binding of sulfated LMWLs, a panel of site-directed thrombin mutants was studied. Substitution of alanine for Arg(93) or Arg(175) induced a 7-8-fold decrease in inhibition potency, while Arg(165)Ala, Lys(169)Ala, Arg(173)Ala and Arg(233)Ala thrombin mutants displayed a 2-4-fold decrease. Other exosite 2 residues including those that play an important role in heparin binding, such as Arg(101), Lys(235), Lys(236) and Lys(240), did not induce any deficiency in sulfated LMWL activity. Thrombin mutants with multiple alanine substitution of basic residues showed a progressively greater defect in inhibition potency. Comparison of thrombin, factor Xa, factor IXa and factor VIIa primary sequences reiterated Arg(93) and Arg(175) as residues likely to be targeted by sulfated LMWLs. The identification of a novel site on thrombin with capability of allosteric modulation is expected to greatly assist the design of new regulators based on the sulfated LMWL scaffold.
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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.