KINETICS AND MECHANISM OF THE REVERSIBLE ISOMERIZATION OF ASPARTIC-ACID RESIDUES IN TETRAPEPTIDES

Citation
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
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry Physical","Chemistry Inorganic & Nuclear
Journal title
ISSN journal
0300-9580
Issue
3
Year of publication
1995
Pages
437 - 442
Database
ISI
SICI code
0300-9580(1995):3<437:KAMOTR>2.0.ZU;2-4
Abstract
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.