Binding of hirudin to meizothrombin

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Binding of hirudin to meizothrombin.

Prothrombin (coagulation factor II) is the inactive precursor molecule of thrombin (coagulation factor IIa). Proteolytic cleavage of the peptide bond Arg320-Ile321 converts prothrombin into the two-chain thrombin precursor meizothrombin. Meizothrombin hydrolyses peptidyl substrates, but cleavage of fibrinogen is poor. Unfortunately, meizothrombin exhibits a significant autocatalytic activity an...

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General numerical treatment of competitive binding kinetics: application to thrombin-dehydrothrombin-hirudin.

This paper describes a general numerical method for the determination of rate constants that characterize the binding of a ligand L simultaneously and competitively to two different receptor molecules, R1 and R2. The experimental data consist of changes in the concentration of one receptor (e.g., R1) monitored over time. An example problem is represented by hirudin (L) binding to thrombin (R1) ...

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Catabolism of hirudin and thrombin-hirudin complexes in the rat.

The metabolic fate of the anticoagulant protein, hirudin, and its complex with thrombin are presently unknown. Therefore we have labelled hirudin and human thrombin-hirudin complex with the residualizing label dilactitol-125I-tyramine (*I-DLT) in order to identify their tissue sites of catabolism in the rat. The rapid plasma clearance of hirudin after intravenous injection was unaffected by *I-...

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Modified plasma-based ecarin clotting time assay for monitoring of recombinant hirudin during cardiac surgery.

Recombinant hirudin (r-hirudin) is being used increasingly for therapeutic anticoagulation in patients with heparin-induced thrombocytopenia undergoing cardiovascular surgery. Although multiple laboratory methods are available for measuring r-hirudin, the ecarin clotting time (ECT) is the most commonly used for this purpose. Ecarin (extracted from snake venom) converts prothrombin to meizothrom...

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Inhibition With Hirudin

Background The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, ...

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ژورنال

عنوان ژورنال: Protein Engineering Design and Selection

سال: 1998

ISSN: 1741-0126,1741-0134

DOI: 10.1093/protein/11.8.715