Mechanism of 2,5-dioxopiperazine formation
Mechanism of 2,5-dioxopiperazine formation
复制标题
DOI：
10.1021/ja972051a
复制
发表时间：
1998-03-11
影响因子：
15
通讯作者：
Mazzarella, L
中科院分区：
文献类型：
--
作者：
Capasso, S;Vergara, A;Mazzarella, L
H-Ala-Pro-NH 2环化为2，5-二氧代哌嗪（DKP）已被研究为可在多肽链的N-末端发生的肽键自发切割伴随2，5-二氧代哌嗪形成的模型。该反应涉及N-末端氨基对第二个残基的羰基碳的预平衡攻击，得到两性离子环状中间体T+/-，其处于酸碱平衡，具有以不同质子化等级T-0、T+和T-为特征的各种形式。碱-催化和pH-速率曲线的布朗斯台德图分别给出平衡T- + H+可逆箭头T+/-和T- + H+可逆箭头T-0的pK（a）类似于7和类似于13。该反应受一般碱和一般酸催化，作用于不同的步骤。氨基从T-0和T-通过两条平行的路线离开，得到产物。双功能酸催化剂HCO 3-强烈地增加反应速率，并且在高浓度下引起限速步骤的变化。在高pH下，总反应速率受到Ala-Pro肽键的反式-->顺式异构化的限制。
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 bond with concomitant formation of 2,5-dioxopiperazine that can occur at the N-terminus of a polypeptide chain. The reaction involves pre-equilibrium attack of the N-terminal amino group on the carbonyl carbon of the second residue giving a zwitterionic cyclic intermediate, T+/-, which is in acid-base equilibrium with various forms characterized by different 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 general base and general acid catalysis, acting on different steps. Departure 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 rate-limiting step. At high pH, the overall reaction rate is limited by the trans --> cis isomerization of the Ala-Pro peptide bond.