Developing peptide inhibitors to thrombin activation of platelets from bradykinin analogs.

  title={Developing peptide inhibitors to thrombin activation of platelets from bradykinin analogs.},
  author={Ahmed Abbas Hasan and Mark Warnock and Sujata Srikanth and Alvin H. Schmaier},
  journal={Thrombosis research},
  volume={104 6},

Synthesis and Characterization of Novel Unnatural Peptide Inhibitors of Thrombin Activation of Platelet Aggregation.

Compound 27, which completely inhibits threshold γ-thrombin-induced platelet aggregation at a concentration of 16 μM, represents an important lead compound in the development of inhibitors of thrombin -mediated platelets aggregation.

The Preparation and Characterization of Novel Peptide Antagonists to Thrombin and Factor VIIa and Activation of Protease-Activated Receptor 1

Thrombin and protease-activated receptor 1 (PAR1) activation antagonists were prepared based upon the peptide RPPGF, the angiotensin-converting enzyme breakdown product of bradykinin. A library of 72

Synthesis of Novel Peptide Inhibitors of Thrombin‐induced Platelet Activation

FM19, which completely inhibits threshold γ‐thrombin‐induced platelet aggregation at a concentration of 16 ± 4 μm, represents an important lead compound in the development of inhibitors of thrombin-mediated platelet aggregating for treatment of ACS.


These investigations indicate that prevention of thrombin cleavage of PAR1 and 4 also is an appropriate target to develop anti-thrombin, anti-platelet agents and suggest that RPPGF and related compounds are novel antagonists to throm bin, factor VIIa, andThrombin activation of platelets.

Thrombostatin FM compounds: direct thrombin inhibitors – mechanism of action in vitro and in vivo

FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add‐on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current antiplatelet therapy still have reactive platelets.

Crosstalk between coagulation and inflammation in mastitis and metritis in dairy cows.

The excessive production of thrombin not only causes hypercoagulatory disorders but also exaggerates neutrophil function by the release of some enzymes which may play a destructive role during disseminated intravascular coagulation (DIC).



Bradykinin and its metabolite, Arg-Pro-Pro-Gly-Phe, are selective inhibitors of alpha-thrombin-induced platelet activation.

Results indicate that bradykinin and its metabolites are selective antithrombins by preventing alpha-thrombin cleavage of the cloned thrombin receptor between arginine-41 and serine-42.

Selection of a Suppressor Mutation That Restores Affinity of an Oligonucleotide Inhibitor for Thrombin Using in Vitro Genetics (*)

Results provide insight into the aptamer-thrombin interaction and suggest that the binding site for the prototype is the dominant aptamorigenic site on thrombin.

Factor XI activation in a revised model of blood coagulation

A revised model of coagulation is proposed in which factor XI is activated by thrombin, and part of this effect is due to autoactivation of factor XI by activated factor XI.

Miniglucagon [glucagon-(19-29)] is a component of the positive inotropic effect of glucagon.

It is concluded that glucagon processing into miniglucagon may be essential for the positive inotropic effect of glucagon on heart contraction.

Muscarinic receptor regulation of cytoplasmic Ca2+ concentrations in human SK-N-SH neuroblastoma cells: Ca2+ requirements for phospholipase C activation.

Results indicate that the magnitude of the initial rise in [Ca2+]i is directly related to the production of phosphoinositide-derived second messenger molecules and that the phospholipase C-mediated breakdown of inositol lipids in SK-N-SH cells is particularly sensitive to regulation by physiologically relevant Ca2+ concentrations.

The use of synthetic peptide combinatorial libraries for the identification of bioactive peptides.

Examples are presented in which an SPCL, composed in total of 52,128,400 acetylated hexa-peptides, is used along with an iterative selection process to precisely identify the antigenic determinant of a peptide recognized by a monoclonal antibody using competitive enzyme-linked immunosorbent assay.

A new generation of Ca2+ indicators with greatly improved fluorescence properties.

A new family of highly fluorescent indicators has been synthesized for biochemical studies of the physiological role of cytosolic free Ca2+ using an 8-coordinate tetracarboxylate chelating site with stilbene chromophores that offer up to 30-fold brighter fluorescence.