ENZYMATIC SYNTHESIS OF SPECIFIC DIPEPTIDES FOR NUTRITION

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DESCRIPTION: (Adapted from the investigator's abstract.) Recent investigations indicate that dipeptides may have several advantages over free amino acids as the nitrogen source in therapeutic enteral and parenteral nutrition. If the use of synthetic dipeptides is to be investigated completely and ultimately incorporated into medical practice, it is necessary to have a cost-effective method for synthesizing specific dipeptides. However, available peptide-synthesis techniques have serious drawbacks. The drawbacks include racemization of components during coupling and deprotection reactions, the high cost and potential environmental hazards posed by the reagents used, and the expensive and time consuming purification steps required after each step. This project is directed at demonstrating the feasibility of a simplified and economical peptide-synthesis procedure. The process is based on enzyme-catalyzed reactions that overcome the disadvantages of conventional synthesis techniques. The objectives of this Phase I program are threefold: 1) to demonstrate that the proposed system can synthesize and deprotect three target dipeptides, 2) to test the performance of the system at a preparative scale, and 3) to conduct a preliminary assessment of the economics of the proposed system. Success in Phase I would lead to a Phase II proposal focused on expansion of the technology to a wider range of dipeptides, optimization of the proposed process, and a detailed economic analysis of the entire integrated system.