KINETICS AND MECHANISM OF SUCCINIMIDE RING FORMATION IN THE DEAMIDATION PROCESS OF ASPARAGINE RESIDUES

Citation
S. Capasso et al., KINETICS AND MECHANISM OF SUCCINIMIDE RING FORMATION IN THE DEAMIDATION PROCESS OF ASPARAGINE RESIDUES, Perkin transactions. 2, (4), 1993, pp. 679-682
Citations number
25
Language
INGLESE
art.tipo
Article
Journal title
ISSN journal
0300-9580
Issue
4
Year of publication
1993
Pages
679 - 682
Database
ISI
SICI code
0300-9580(1993):4<679:KAMOSR>2.0.ZU;2-V
Abstract
The cyclization of Ac-Gly-Asn-Gly-Gly-NHMe to the succinimide derivati ve has been studied in the pH range 5.5-10.4 at 37-degrees-C and mu = 1 mol dm-3. Kinetic evidence indicates that the reaction is a multiste p process with a change in the rate-determining step at pH 6.5-7.0. Th e suggested mechanism involves the pre-equilibrium deprotonation of th e NH group next to the Asn residue, followed by nucleophilic attack of the nitrogen atom on the carbonyl carbon of the Asn side chain giving a cyclic tetrahedral intermediate. At acidic pH the cyclization step is rate determining, whereas, the removal of the leaving group by appa rent general-base catalysis is the rate-determining step at neutral an d basic pH. The literature data on the deamidation rate are discussed in light of the proposed mechanism.