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
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.