ENZYMATIC SYNTHESIS OF SPECIFIC DIPEPTIDES FOR NUTRITION

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 INVESTITAGED 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 SIMPLIFED AND ECONOMICAL PEPTIDE-SYNTHESIS PROCEDURE. THE PROCESS IS BASED ON ENZYME-CATALYZED RACTIONS THAT OVERCOME THE DISADVANTAGES OF CONVENTIONAL SYNTEHSIS TECHNIQUES. THE OBJECTIVES ARE THREEFOLD: (1) TO DEMONSTRATE THAT THE 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 SYSTEM. SUCCESS IN PHASE I WOULD LEAD TO A PHASE II EFFORT FOCUSED ON EXPANSION OF THE TECHNOLOGY TO A WIDER RANGE OF DIPEPTIDES, OPTIMIZATION OF THE PROCESS, AND A DETAILED ECONOMIC ANALYSIS OF THE ENTIRE INTEGRATED SYSTEM.