S. Capasso et al., KINETICS AND MECHANISM OF THE REVERSIBLE ISOMERIZATION OF ASPARTIC-ACID RESIDUES IN TETRAPEPTIDES, Perkin transactions. 2, (3), 1995, pp. 437-442
The influence of pH and buffer concentration on the rate of the isomer
ization of Asp residues has been analysed using model aspartic acid-co
ntaining tetrapeptides, in the pH range 1.5-10 at 37 degrees C and mu
= 1 mol dm(-3). The reaction involves the reversible formation of amin
o-succinimide intermediate. Kinetic evidence indicates that of the-var
ious forms of the Asp-peptide in acid-base equilibrium, only one, havi
ng the carboxylic Asp side chain in the neutral state and the N-H pept
ide group next to the Asp residue in the deprotonated state, reacts at
an appreciable rate. The reaction involves nucleophilic attack by the
nitrogen atom of the peptide bond on the carbonyl carbon of the Asp s
ide chain, giving a cyclic tetrahedral intermediate. At pH values lowe
r than about 3 the cyclization step is rate-determining, but at higher
pH the rate-determining step is the general acid-catalysed departure
of the leaving group. This change of rate-determining step, together w
ith the ionization of the carboxylic side chain of the Asp residue, pr
oduces a bell-shaped curve in the pH-rate profile for the cyclization
reactions.