ENZYME REACTORS FOR THE SYNTHESIS OF PEPTIDE INHIBITORS

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Hypertension is one of the major health challenges facing researchers in pharmaceutical field today. Synthetic peptides that are inhibitors of renin and angiotensin-converting enzyme [ACE] have proved very successful in treating hypertension and have shown promise in treating other disease states. While the demand is high for synthetic peptides to treat hypertension and other disorders, available peptide-synthesis techniques have serious drawbacks. The drawbacks include racemization of components during coupling reactions, the high cost and potential environmental hazards posed by the coupling reagents used, and the expensive and time-consuming purification steps required after each coupling step. This project is directed at demonstrating the feasibility of an improved peptide-synthesis procedure. The process is based on a novel membrane- based enzyme reactor that overcome the disadvantages of conventional synthesis techniques. The objectives of this Phase I program are threefold: 1) to determine the operating conditions required for a membrane-based enzyme reactor for the continuous synthesis of a model peptide, 2) to construct the enzyme reactor, and 3) to test the performance of the system. Success in Phase I would lead to a Phase II program focused on the optimization and scale-up of the proposed process and investigation of additional applications.