The Biosynthesis of Peptide Bonds 107 



densation of two amino acid units to form a peptide bond. Recent 

 studies have demonstrated clearly that this value applies only to the 

 reactions for which it was determined, the synthesis of a dipolar di- 

 peptide ion from the component amino acid ions (cf. Table 1). Thus, 

 in a condensation reaction leading to the formation of an uncharged 

 peptide, the value for ±F° may be as small as +0.4 kcal. 1 On the 

 other hand, a condensation reaction in which an acylamino acid is 

 converted to the corresponding amide may be characterized by a ±F° 

 value much higher than +3 kcal.; this is suggested by the A// values 

 cited in Table 1. Although more data are needed for the thermo- 



Table 1. Thermodynamic Relations in the Synthesis of Some 

 CO-NH Bonds 



Reaction 

 DL-Leucine* + Glycine* — * DL-leucylglycine* + H2O 

 Benzoyl-L-tyrosine - + Glycinamide + — > Benzoyl- 



i>tyrosylgIycinamide + H-jO 

 Benzoyl-L-tyrosine - + NH.i + — > Benzoyl-L-tyrosin- 



amide + H2O 

 Glycyl-L-phenylalanine* + NH4 + — > Glycyl- 



L-phenylalanmamide + H2O 



dynamics of peptide formation, the available information is sufficient 

 to indicate the oversimplification inherent in the assignment of an 

 arbitrary value of -f 3 kcal. per mole to the synthesis of the CO-NH 

 bonds of proteins. It may in fact be expected that, if two peptides 

 of moderate length were converted to a single long-chain peptide in a 

 condensation reaction, the energy required would be much less than 

 3 kcal. 



Since thermodynamic data only can tell us what may happen, but 

 give no information about what does happen in a living cell, the only 

 general conclusion that can be drawn from the available AF° values 

 is that, at pH 7, the formation of a peptide bond by a condensation 

 reaction is an endergonic process. These data do not rule out the 

 physiological occurrence of such reactions, especially if the union of 

 two peptides of moderate chain length is considered. In the absence 

 of experimental evidence to the contrary, it would seem premature to 

 discard the possibility of condensation reactions, as has been suggested 

 at various times. Of special relevance is the consideration that the 

 living cell is not a homogeneous system in which the chemical reactants 

 are present in equilibrium concentrations. Hence, it seems reasonable 

 to envisage the enzyme-catalyzed formation of interior peptide bonds 



