MECHANISM OF 2,5-DIOXOPIPERAZINE FORMATION

Citation
S. Capasso et al., MECHANISM OF 2,5-DIOXOPIPERAZINE FORMATION, Journal of the American Chemical Society, 120(9), 1998, pp. 1990-1995
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry
ISSN journal
0002-7863
Volume
120
Issue
9
Year of publication
1998
Pages
1990 - 1995
Database
ISI
SICI code
0002-7863(1998)120:9<1990:MO2F>2.0.ZU;2-S
Abstract
The cyclization of H-Ala-Pro-NH2 to the 2,5-dioxopiperazine (DKP) has been studied as a model for the spontaneous cleavage of the peptide bo nd with concomitant formation of 2,5-dioxopiperazine that can occur at the N-terminus of a polypeptide chain. The reaction involves pre-equi librium attack of the N-terminal amino group on the carbonyl carbon of the second residue giving a zwitterionic cyclic intermediate, T+/-, w hich is in acid-base equilibrium with various forms characterized by d ifferent grades of protonation, T-0, T+ and T-. The Bronsted plot for the base-catalysis and the pH-rate profile give pK(a) similar to 7 and similar to 13 for the equilibria T- + H+ reversible arrow T+/- and T- + H+ reversible arrow T-0, respectively. The reaction is subject to g eneral base and general acid catalysis, acting on different steps. Dep arture of the amino group from T-0 and T- by two parallel routes gives the product. The bifunctional acid catalyst HCO3- strongly increases the reaction rate and at high concentrations causes a change of the ra te-limiting step. At high pH, the overall reaction rate is limited by the trans --> cis isomerization of the Ala-Pro peptide bond.