Intrinsic Dissociation Constants of Aspartyl and Glutamyl Carboxyl Groups

The synthesis of N-acetyl-l-isoasparagine and of N-acetyl-l-isoglutamine is reported. The acid dissociation constants of these compounds, and those of their corresponding N-carbobenzoxy derivatives, have been measured. Since these compounds are uncharged molecules of the type —NH—CH(—CH2COOH)—CO— or the corresponding glutamyl homologue, their dissociation constants represent the intrinsic dissociation constants of aspartyl and glutamyl side chains in polypeptide chains. Additional values for these constants were obtained from pK values of charged molecules of the same type, after calculating corrections for the effects of the charges. All results obtained in this way are consistent, and indicate that aspartyl carboxyl groups are significantly more acidic than glutamyl carboxyl groups. Intrinsic pK values at 25° and zero ionic strength are 4.08 ± 0.05 for aspartyl groups and 4.50 ± 0.06 for glutamyl groups.