| emostasis arrests bleeding from injured vessels. The physiologically useful functions of hemostasis can also contribute to thrombosis. Inhibition of platelet functions and blood clotting mechanisms is a very important approach for prevention of thrombosis. This dissertation describes the anti-hemostatic functions and specificities of synthetic peptides and peptides isolated from ticks.;Papers I and II deal with the search for anti-hemostatic substances from the hematophagous hard tick Dermacentor variabilis. An anti-platelet peptide and an anti-coagulation peptide have been isolated from salivary glands of the ticks using a combination of size-exclusion chromatography and high pressure liquid chromatography. The purified anti-platelet peptide ("variabilin") is a potent inhibitor of platelet aggregation and an antagonist of platelet membrane protein ;The isolation and partial sequence of an inhibitor of factor Xa in blood coagulation are described in Paper II. The inhibitor seems to have two forms, with molecular weights of 5940 and 6070, respectively. The sequence of amino terminal 50 amino acid residues of this 55 residue protein was determined by the Edman degradation method. This sequence has no significant homology to other known proteins.;The specificities of natural and synthetic anti-hemostatic peptides were addressed in Papers I and III, respectively. The ability of variabilin to block adhesion of osteosarcoma cells to immobilized vitronectin indicates that variabilin is also an antagonist of vitronectin receptor... |
