Potent Trivalent Inhibitors of Thrombin through Hybridization of Salivary Sulfopeptides from Hematophagous Arthropods

The rational design of a novel class trivalent thrombin inhibitors is described through the hybridization natural sulfopeptides produced by blood feeding organisms. hybrid were rapidly assembled using peptide ligation chemistry and shown to exhibit femtomolar inhibition constants against thrombin. A lead inhibitor also showed potent generation platelet aggregation in vitro, as well antithrombotic effects murine model.