BackgroundFactor VIII (FVIII) is activated by thrombin‐catalyzed cleavage at three sites. Previous reports indicated that the A2 domain contained thrombin‐interactive sites responsible for Arg372. We have also found A1 of FVIII bound to anion‐binding exosite I thrombin. The present study focused, therefore, on thrombin interaction with residues 337‐372 containing clustered acidic and hirugen‐li...

Thrombin facilitates the aggregation of platelet in hemostatic processes and participates regulation cell signaling. Therefore, development thrombin sensors is conducive to comprehending role course a disease. Biosensors based on aptamers screened by SELEX have exhibited superiority for detection. In this review, we summarized aptamer-based detection which rely specific recognitions between apt...

We previously postulated that thrombin might initiate platelet aggregation and the release reaction by acting at the platelet surface. We have now demonstrated surface binding of thrombin using highly purified bovine thrombin labeled with lzsI. At least two classes of binding sites have been demonstrated. When studies are done at relatively high thrombin concentrations, platelets bind 50,000 th...

The prothrombinase complex converts prothrombin to α-thrombin through the intermediate meizothrombin (Mz-IIa). Both α-thrombin and Mz-IIa catalyze factor (F) XI activation to FXIa, which sustains α-thrombin production through activation of FIX. The interaction with FXI is thought to involve thrombin anion binding exosite (ABE) I. α-Thrombin can undergo additional proteolysis to β-thrombin and γ...

To determine the relationship between equilibrium binding of thrombin to sites on the platelet surface and the cleavage of membrane glycoprotein V (GPV) by thrombin, we examined the effect of active site-modified thrombin (1-chloro-3-tosylamido-7-amino-L-2-heptanone thrombin toslysCH2-thrombin) on the binding of native thrombin to platelets and on the hydrolysis of GPV by native thrombin. Tosly...

Human thrombin binds to specific receptors on the surface of human platelets in a manner analogous to bovine thrombin. Thus, two classes of binding are observed--high affinity with a dissociation constant (Kdiss) of 0.02 U/ml and low affinity with a Kdiss of 5 U/ml. Bovine and human thrombin bind to the same platelet receptors, although bovine thrombin binds with slightly greater affinity. When...

Based on the structure of natural product andrographolide, a series novel 12-quinoline substituted derivatives 9 were designed and synthesized. In preliminary biological evaluation, these synthesized compounds showed prominent anti-platelet aggregation activities in response to thrombin adenosine diphosphate (ADP) agonists. Among them, compound 9o (inhibition rate 55.73%, IC50 0.36 µM/L) had hi...

Competition binding studies have been carried out to evaluate the antagonism of TLCK-thrombin (N“-tosylL-lysine chloromethyl ketone-treated thrombin) and PPACK-thrombin (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone-treated thrombin) with athrombin using computer-assisted analysis of the binding isotherms (LIGAND). &-Thrombin bound to high, moderate, and low affinity sites as previousl...

Platelet activation by thrombin plays a critical role in hemostasis and thrombosis. Based on structure-activity studies of a cloned platelet thrombin receptor, we designed two "mirror image" antagonists of thrombin and thrombin receptor function. First, "uncleavable" peptides mimicking the receptor domain postulated to interact with thrombin were found to be potent thrombin inhibitors. Second, ...