Stability of hirudin, a thrombin-specific inhibitor. The structure of alkaline-inactivated hirudin
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چکیده
منابع مشابه
Stability of Hirudin, a Thrombin-specific Inhibitor
Hirudin is a 65-amino acid polypeptide with three disulfide linkages. It is stable under extreme pH (1.4712.9), high temperature (95 “C), and in the presence of denaturants (6 M guanidinium chloride or 8 M urea). The thrombin inhibitory activity of hirudin remains unaffected even after cleavage of an internal peptide bond ( L y ~ ~ ‘ A s n ~ ~ ) . One condition which effectively and irreversibl...
متن کاملThe direct thrombin inhibitor hirudin.
This review discusses the pharmacology and clinical applications of hirudin, a bivalent direct thrombin inhibitor (DTI). Besides the current major indication for hirudin--anticoagulation of patients with heparin-induced thrombocytopenia (HIT)--the experience with hirudin in other indications, especially acute coronary syndromes, are briefly presented. Hirudins have been formally studied prior t...
متن کاملCatabolism 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-...
متن کاملIonic interactions in the formation of the thrombin-hirudin complex.
Site-directed mutagenesis has been used to examine the importance of each of the acidic C-terminal residues of hirudin in the formation of its complex with alpha-thrombin. The contribution to binding energy of acidic residues in the 11 C-terminal amino acids varied from 2.3 to 5.9 kJ.mol-1. The differences between the contributions of individual residues were smaller than would be expected from...
متن کاملPersistent thrombin generation in humans during specific thrombin 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 3- to 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: Journal of Biological Chemistry
سال: 1991
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(18)99095-2