Title Monitoring Protamine‐Heparin Interactions Using Microcapillary Impedimetric Sensor

Abramova, Natalia; Bratov, Andrey

doi:10.1002/elan.201400581

Cited by 8 publications

(6 citation statements)

References 28 publications

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“…The negatively charged polyanion ligand PPS will then electrostatically interact with the positively charged protamine and form a second layer, which is now negatively charged, thus producing a cathodic EOF. A similar deposition of protamine and heparin layers has been observed on silicon oxide surfaces of microcapillary impedimetric sensors monitoring protamineheparin interactions [71]. As the reaction between heparin and protamine is irreversible, it may be concluded, that the injected PPS ligand will also be bound tightly to the protamine layer on the one side and form strongly negatively charged complexes with free protamine on the other side, so that no protamine peak can be detected.…”

Section: Interaction Of Pps With Protamine Sulfatesupporting

confidence: 58%

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p‐selectin and other proteins

et al. 2017

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A fast and precise affinity capillary electrophoresis (ACE) method has been developed and applied for the investigation of the binding interactions between P-selectin and heparinoids as potential P-selectin inhibitors in the presence and absence of calcium ions. Furthermore, model proteins and vitronectin were used to appraise the binding behavior of P-selectin. The normalized mobility ratios (∆R/R ), which provided information about the binding strength and the overall charge of the protein-ligand complex, were used to evaluate the binding affinities. It was found that P-selectin interacts more strongly with heparinoids in the presence of calcium ions. P-selectin was affected by heparinoids at the concentration of 3 mg/L. In addition, the results of the ACE experiments showed that among other investigated proteins, albumins and vitronectin exhibited strong interactions with heparinoids. Especially with P-selectin and vitronectin, the interaction may additionally induce conformational changes. Subsequently, computational models were applied to interpret the ACE experiments. Docking experiments explained that the binding of heparinoids on P-selectin is promoted by calcium ions. These docking models proved to be particularly well suited to investigate the interaction of charged compounds, and are therefore complementary to ACE experiments.

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Section: Interaction Of Pps With Protamine Sulfatesupporting

confidence: 58%

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p‐selectin and other proteins

et al. 2017

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“…However, the data on the physicochemical characterization of the protamine–heparin complex remain limited since it was first characterized by Abramova et al. [29]. Thus, in the present study, protamine was replaced with a better defined tetraarginine peptide.…”

Section: Introductionmentioning

confidence: 90%

Interaction of heparin and tetraarginine in capillary electrophoresis: Implication for analytical applications

et al. 2020

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Interactions between heparin and tetraarginine in an acidic background electrolyte were investigated in capillary electrophoresis. The results showed that tetraarginine and heparin form a stable complex that migrates toward the anode immediately after coming into contact. When a zone of tetraarginine at a mg/mL concentration level passes through a zone of heparin at a μg/mL concentration level, tetraarginine is gradually removed by the formation of the complex that migrates in the opposite direction, thereby decreasing the tetraarginine peak area. The variation of the tetraarginine peak area as a function of the unfractionated heparin concentration was linear within the range 2–20 μg/mL, which enables us to detect and determine heparin concentrations undetectable with a UV detector. The same behavior was confirmed for low molecular weight heparin.

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“…A similar static strategy involved protamine adsorbed on the silicon oxide surface of a microcapillary impedimetric sensor. 74 Heparin binding resulted in surface charge alteration that could be monitored by measuring the device impedance in buffer.…”

Section: (Poly-)peptidic Bindersmentioning

confidence: 99%

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

Ourri

Vial

2019

ACS Chem. Biol.

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The heparin family, which includes unfractionated heparin, low-molecular heparin and fondaparinux, is a class of drugs clinically used as intravenous blood thinner. To date, issues related to both to the reversal of anticoagulation and the blood level determination of the anticoagulant at the point-of-care remain: while the only U.S. Food and Drug Administration (FDA) approved antidote for heparin displays serious efficacy and safety drawbacks, the current assays for heparin monitoring are indirect measurements subject to their own limitations and variations. Herein, we provide an update on the numerous recent chemical approaches to tackle these issues, from which it is clear that some new antidotes and sensors for heparin certainly have the potential to exceed current clinical standards. This review aims to review a field that requires close collaborations between physicians, biologists and chemists in order to foster advances toward clinical translation. Context and challengesHeparin, which belongs to the family of glycosaminoglycans (GAGs), is a linear sulfated polysaccharide and consists of repeating disaccharide subunits of α-1,4 linked uronic acid and D-glucosamine (Figure 1). As a consequence, heparin displays the highest density of negative charges among biomacromolecules. This polyanion is widely used as an intravenous anticoagulant due to its ability to accelerate the rate at which antithrombin (AT) inhibits serine proteases within the blood coagulation cascade, most notably factor Xa and thrombin. [1][2][3][4] Polymers of various lengths such as unfractionated heparin (UFH, Mw ~ 15 kDa), low-molecular-weight heparins (LMWHs, Mw = 3.6-6.5 kDa), and the synthetic pentasaccharide fondaparinux (Mw = 1.7 kDa) are routinely delivered to patients. While UFH is used during acute thrombotic events or to maintain blood fluidity during procedures requiring extracorporeal circulation (i.e., cardio-pulmonary bypass or hemodialysis), 5,6 LMWHs and fondaparinux are prescribed to treat and/or prevent deep vein thrombosis and pulmonary embolism. 7,8 With an estimated one billion doses of heparin produced every year, heparin's market is rapidly growing, driven by the ageing of populations and the increasing incidence of cardiovascular diseases. 9 KeywordsAnticoagulants: commonly known as blood thinners, they are chemical substances that retard or inhibit the coagulation of the blood.

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Title Monitoring Protamine‐Heparin Interactions Using Microcapillary Impedimetric Sensor

Cited by 8 publications

References 28 publications

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p‐selectin and other proteins

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p‐selectin and other proteins

Interaction of heparin and tetraarginine in capillary electrophoresis: Implication for analytical applications

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

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