Heats of hydrolysis of amide and peptide bonds.

The thermodynamics of amide and peptide bonds is of fundamental importance in the study of the synthesis and breakdown of proteins in biological systems. One of the necessary steps in acquiring significant thermodynamic data in this field is the determination of the changes in heat content accompanying the formation or rupture of such bonds in compounds of known structure. We have accordingly undertaken a program of calorimetric measurements of the heats of hydrolysis of various synthetic peptides.l In the present paper we shall outline the method of experimentation and report results obtained for the hydrolysis of carbobenzoxyglycyl-L-phenylalanine (CGP) catalyzed by carboxypeptidase and of benzoyl-L-tyrosinamide (BTA) catalyzed by chymotrypsin. Determination of Heats of Hydrolysis-There are three general methods available for the estimation of the heats of organic reactions. The classical procedure involves the determination of the heats of combustion of the reactants and the products, the heat of reaction being equal to the sum of the heats of combustion of the products less the corresponding sum for the reactants. The outstanding limitation of this method, in the present connection, is that the resultant enthalpy change refers to a hypothetical process, involving reactants and products in their combustion standard states (usually pure solid or liquid compounds), which has but little resemblance to the process taking place in biological systems. The various heats of solution necessary to convert such an enthalpy change to a value pertaining to a reaction in solution are not as a rule available. Huffman (1) and his coworkers have applied this method in several cases to obtain results which may be typified by the following equation.