Thrombin Inhibitors from Different Animals

Tanaka-Azevedo, Anita Mitico; Morais-Zani, Karen de; Torquato, Ricardo J.S.; Tanaka, Aparecida S.

doi:10.1155/2010/641025

Cited by 30 publications

(21 citation statements)

References 107 publications

(103 reference statements)

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“…The formation of thrombosis is a very complex pathological process involving the platelets and blood coagulation components. Thrombin plays a vital role in blood coagulation by promoting platelet aggregation and by converting fibrinogen to form the fibrin clot in the final step of the coagulation cascade [ 2 ]. Thrombin is composed of two polypeptide chains of 36 (A chain) and 259 (B chain) residues that are covalently linked through a disulfide bond, and the B chain carries the functional epitopes of the enzyme [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

Yang

et al. 2018

Journal of Analytical Methods in Chemistry

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Thrombin plays a vital role in blood coagulation, which is a key process involved in thrombosis by promoting platelet aggregation and converting fibrinogen to form the fibrin clot. In the receptor concept, drugs produce their therapeutic effects via interactions with the targets. Therefore, investigation of interaction between thrombin and small molecules is important to find out the potential thrombin inhibitor. In this study, affinity capillary electrophoresis (ACE) and in silico molecular docking methods were developed to study the interaction between thrombin and ten phenolic compounds (p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, catechin, epicatechin, dihydroquercetin, naringenin, apigenin, and baicalein). The ACE results showed that gallic acids and six flavonoid compounds had relative strong interactions with thrombin. In addition, the docking results indicated that all of optimal conformations of the six flavonoid compounds were positioned into the thrombin activity centre and had interaction with the HIS57 or SER195 which was the key residue to bind thrombin inhibitors such as argatroban. Herein, these six flavonoid compounds might have the potential of thrombin inhibition activity. In addition, the developed method in this study can be further applied to study the interactions of other molecules with thrombin.

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Section: Introductionmentioning

confidence: 99%

Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

Yang

et al. 2018

Journal of Analytical Methods in Chemistry

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“…DOACs fall into 2 categories—factor IIa (thrombin) inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, and betrixaban). Direct thrombin inhibitor, hirudin, was first isolated from leech saliva, whereas factor Xa inhibitor, TIX-5, was first discovered from tick saliva [ 7 ]. The first medication of the DOAC group to be approved by the United States Food and Drug Administration (FDA) was dabigatran etexilate (Pradaxa) (Boehringer Ingelheim Pharmaceuticals, Inc.) in October 2010, and this is a direct thrombin inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Dabi

Koutrouvelis²

2018

Critical Care Research and Practice

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Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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“…The inhibitory salivary gland peptide in the present study might be helping ticks to feed on blood of host by overcoming the host's hemostatic mechanism involving thrombin. Since direct thrombin inhibitors are a new class of anticoagulants that bind directly to thrombin and block its interaction with its substrates (Tanaka-Azevedo et al,2010). These inhibitors depend on the interaction among thrombin exosites and the substrates on platelet membrane, namely platelet activating receptors-1 and platelet activating receptors-4 (Ofosu, 2003;Huntigton, 2005).…”

Section: Resultsmentioning

confidence: 99%

Molecular characterization of anti-platelet aggregating proteins in salivary gland extracts of Hyalomma anatolicum ticks

Sangwan

Surbhi

Sangwan

2018

IJAR

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Tick saliva is a cocktail of potent anti-haemostatic, anti-inflammatory and immunomodulatory molecules that help the ticks to obtain a blood meal from their vertebrate hosts. Thrombin is considered as an activator for stimulation of blood platelets at different receptor sites and thrombin induced platelet aggregation depends on the interaction among thrombin exosites and the receptors on platelet membrane. Thus, the present study was planned to isolate and characterize the salivary antiplatelet aggregating proteins from Hyalomma anatolicum ticks. A hundred pairs of salivary glands were dissected out and extract was prepared by fractionation of proteins by gel filtration chromatography. The fractions so obtained were tested for thrombin induced platelet aggregation and platelet-collagen adhesion inhibition activities. Proteins in fraction nos. 28, 29, 30, 31, 32, 42, 58, 111 and 112 were found to inhibit platelet aggregation. These proteins also showed significant inhibitory effects on platelet adhesion to collagen when compared to agonist thrombin. This indirectly indicates inhibition of glycoprotein 1b (GP1b), glycoprotein VI (GPVI) and integrin 21 receptors of platelets as these proteins are involved in aggregation of platelets for formation of platelet plug. On electrophoretic separation of fractions by SDS-PAGE, the proteins/peptides present in initial fractions were having approximate molecular weight in the range of 6.5 to 113.4kDa. However, in the fraction no. 112 only single prominent protein band of approximate 65.4kDa was present and is expected to inhibit platelet aggregation possibly through inhibition of platelet receptors such as proteins platelet activating receptors-1 and 4 playing direct role in platelet aggregation. In conclusion, there are possibilities of exploring these anti-platelet aggregating proteins/peptides for therapeutics against cardio-vascular disorders as well as for raising anti-tick vaccine.

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Thrombin Inhibitors from Different Animals

Cited by 30 publications

References 107 publications

Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Molecular characterization of anti-platelet aggregating proteins in salivary gland extracts of Hyalomma anatolicum ticks

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