These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Design and synthesis of a kininogen-based selective inhibitor of thrombin-induced platelet aggregation.
    Author: Matsueda R, Umeyama H, Puri RN, Bradford HN, Colman RW.
    Journal: Pept Res; 1994; 7(1):32-5. PubMed ID: 8019060.
    Abstract:
    Thrombin-induced platelet aggregation has been suggested to play an important role in reocclusion following thrombolytic therapy or angioplasty for treatment of myocardial infarction. We previously demonstrated that thrombin-induced platelet aggregation is indirectly mediated by intracellularly activated calpain expressed on the platelet surface through the cleavage of aggregin, a putative ADP-receptor, and that high molecular weight kininogen (HK), a naturally occurring thiol protease inhibitor, modulates thrombin-induced platelet aggregation. Considering the substrate specificity of calpain and the conserved sequence in HK, we studied selective inhibitors of thrombin-induced platelet aggregation by the affinity labeling approach with an S-3-nitro-2-pyridinesulfenyl (Npys) group. H-Phe-Gln-Val-Val-Cys (Npys)-Gly-NH2, which combines chemical and structural features of calpain substrate specificity and the conserved sequence in HK, selectively inhibited thrombin-induced platelet aggregation. It did not inhibit the aggregatory effects of other platelet agonists, and did not inhibit amidolytic activity of thrombin and thrombin-induced platelet shape change. The design and synthesis of such inhibitors could lead to the development of a new class of inhibitors that selectively block thrombin-induced platelet aggregation.
    [Abstract] [Full Text] [Related] [New Search]