The energetics of peptide bond, formation is an important factor not only in the.design of chemical peptide, synthesis, but it also has a role in protein biosynthesis. In this work, qtantum chemical.calculations at 10 different -leVels of theory, Including G3NIP2B3 were performed on the energetics of glutathione fOrmation. The strength of the peptide bond is found to be ctosely related to the acid strength of the to-be N-terminal and the basicity ofthe to-be C-terminal amino acid: It is shown that the formation of the first pdptide activates the amino acid for the next- condensation step, manifested in bacterial protein synthesis where the first step is the formation of an N-formylmethionine dipeptide. The posSitile role of glutathione in prebiotic molecular evolution is alscr analyzed. The implications of the thermodynamics of peptide- bond formation in prebiotic peptide formation as well as in the preference of alpha- instead of beta- or gamma-amino,acids are discussed. An empirical correction is proposed for the compensation of the error due to the incapability of continuum solvation models in describing, the change of the first,solvation shell when a peptide bond is formed from two zwitterions accompanied by the disappearance of one ion pair.