Comparison of hirudin and hirudin PA C-terminal fragments and related analogs as antithrombin agents.

  title={Comparison of hirudin and hirudin PA C-terminal fragments and related analogs as antithrombin agents.},
  author={John L Krstenansky and Thomas J. Owen and Mark T. Yates and Simon J. T. Mao},
  journal={Thrombosis research},
  volume={52 2},
8 Citations
Thrombin-bound conformation of the C-terminal fragments of hirudin determined by transferred nuclear Overhauser effects.
The interaction of the C-terminal fragments (residues 52-65 and 55-65) of the thrombin-specific inhibitor hirudin with bovine thrombin was studied by use of one- and two-dimensional NMR techniques in
Hirudin was originally isolated from the salivary glands of the medicinal leech Hirudo medicinalis and all of these forms seem to have antithrombin activity and the disulfide bridges and the acidic nature of the molecule, including the sulfated tyrosine, are invariant.
The fibrinogen anion‐binding exosite of thrombin is necessary for induction of rises in intracellular calcium and prostacyclin production in endothelial cells
Thrombin stimulation of prostacyclin (PGI2) synthesis by cultured human umbilical vein endothelial cells (HUVEC) requires the active site of thrombin and involves rapid and transient rises in


Anticoagulant peptides: nature of the interaction of the C-terminal region of hirudin with a noncatalytic binding site on thrombin.
A "kinked" amphipathic alpha-helical structure, which orients all of the residues most critical for activity on one face of the helix, is proposed for anticoagulant activity in hirudin.
Interaction of hirudin with thrombin: identification of a minimal binding domain of hirudin that inhibits clotting activity.
It is shown that the carboxyl-terminal 10 amino acid residues 56-65 are minimally required for binding to thrombin and inhibition of clotting and associated with a significant conformational change of Thrombin as judged by circular dichroism.
Kinetics of the inhibition of thrombin by hirudin.
The dissociation constant for hirudin was determined by varying the concentration of hirUDin in the presence of a fixed concentration of thrombin and tripeptidyl p-nitroanilide substrate and was markedly dependent on the ionic strength of the assay.
Proton Nuclear Magnetic Resonance Study of Hirudin: Resonance Assignment and Secondary Structure?
The /sup 1/H NMR spectrum of the 65-residue protein hirudin is assigned in a sequential manner by using a combination of two-dimensional nuclear magnetic resonance techniques to demonstrate
The conformations of hirudin in solution: a study using nuclear magnetic resonance, distance geometry and restrained molecular dynamics
The solution conformations of the protein hirudin have been investigated by the combined use of distance geometry and restrained molecular dynamics calculations and it appears that the two minor domains exhibit large rigid‐body motions relative to the central core.
Prediction of the secondary structure of proteins from their amino acid sequence.