A NOVEL POTENT NONPEPTIDE MIMETIC BASED ON THE THROMBIN RECEPTOR S42FLLR46 SEQUENCE: RELAXATION AND PLATELET AGGREGATION ACTIVITIES

摘要

Thrombin receptors are attractive drug discovery targets because they mediate a variety of cellular actions of thrombin, such as thrombosis, hemostasis and inflammatory diseases. Thrombin acts on a specific receptor (PAR-1), a member of the seven transmembrane receptor family and causes a limited proteolytic cleavage, leading to the formation of a new N-terminus capable of activating the receptor via intramolecular interaction. Thrombin binds and cleaves the N-terminal exodomain region of LDPR41↓S42FLLR of PAR-1 generating a new N terminus (S42FLLR46) pentapeptide which activates PAR-1 by binding to the body of the receptor. There were several reports that strongly suggest the potential utility of PAR-1 antagonist analogues for the treatment of thrombotic disorders .