The hypothesis of this proposal is that the di- or tri-peptide transporter in the gastrointestinal tract can be used as a means to absorb orally delivered peptides as therapeutics in vivo. Recent information indicates that the bradykinin breakdown product of angiotensin converting enzyme, the pentapeptide Arg-Pro-Pro-Gly-Phe (RPPGF), which we have named "Thrombostatin TM'' has the ability to interact with the extracellular fragment of protease activated receptor 1 (PAR1), the thrombin receptor, to prevent thrombin cleavage and activation. Investigations presently will determine if these anti-thrombin peptides can be orally adsorbed to be active thrombin inhibitors in vivo. The specific aims of this proposal are as follows: Specific aim #1: Evaluate the chemical and enzymatic stability of Thrombostatin TM derivatives in intestinal fluids to create more stable, orally absorbable compounds with increased inhibitory activity. Specific aim #2: Investigations will determine in rats if there is oral absorption of these thrombin inhibitory peptides to act as inhibitors of thrombin activation of platelets. The purpose of these investigations is two-fold. First, investigations will be performed to determine the most stable forms of the RPPGF derivatives that can be absorbed from the gastrointestinal tract. Second, studies will be performed to determine if oral absorption of RPPGF derivatives inhibit thrombin activation of platelets. These investigations aim to develop an oral form of a platelet-selective thrombin inhibitor. Such an agent will be useful in the management of acute coronary syndromes and other disorders of thrombosis.