Studies of the chemical basis of the origin of protein synthesis: initiation and direction of peptide growth.

The data presented in this paper show that the ease of non-enzymatic activation of carboxylic acids by ATP at pH 5 varies directly with the pKa of the carboxyl group, and is consistent with the idea that it is the protonated form of the carboxyl group which participates in the activation reaction. Consequently, since most N-blocked amino acids have higher pKa's than do their unblocked forms, they are activated more readily, and we have demonstrated that this principle applies to peptides as well, which are activated more rapidly than single amino acids. We propose that this fact may be partly responsible for the origin of two important features still observed in contemporary protein synthesis: (1) initiation in prokaryotes is accomplished with an N-blocked amino acid, and (2) elongation in all living systems occurs at the carboxyl end of the growing peptide.