Aspartame Decomposition and Epimerization in the Diketopiperazine and Dipeptide Products as a Function of pH and Temperature.
Aspartame Decomposition and Epimerization in the Diketopiperazine and Dipeptide Products as a Function of pH and Temperature.
复制标题
二酮哌嗪和二肽产品中阿斯巴甜的分解和差向异构化与 pH 和温度的函数关系。
DOI：
10.1002/chin.198848308
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
J. Bada
中科院分区：
文献类型：
--
作者：
S. Gaines;J. Bada
通过使用HPLC方法，可以同时分析非对映体二肽和二酮哌嗪产品，在一定范围的pH值和温度下，研究了环化和水解的阿替西泮。天冬氨酸和苯丙氨酸的消旋速率在二肽二酮哌嗪系统中产生的西司他滨分解的pH依赖性进行了测定。在这些研究的基础上，提出了二酮哌嗪和肽的各种位置和离子状态中氨基酸的相对差向异构化速率的一般方案。根据氨基酸外消旋的碳负离子机理讨论了该方案，发现与之一致，二酮哌嗪的外消旋速率大于所有离子形式的游离氨基酸和二肽，除了完全质子化的游离氨基酸和质子化的肽末端氨基酸。在中性pH范围内，DKP和二肽的相对消旋速率为DKP>氨基端>羧基端。从二肽-二酮哌嗪-转化二肽的转化率方面重新分析了文献中报道的来自二肽加热实验的明显矛盾的结果。从这个角度来看，文献是自洽的，并支持我们的方案的相对消旋率和机理的结论的一般性。二肽及其衍生物的分子内氨解形成环二肽（二酮哌嗪或DKPs）容易发生在水溶液中。1，2这种反应的普遍性对于肽化学和生物化学领域的工作者来说已经变得显而易见。通过在肽的氨基末端形成DKP，内部氨解的快速速率导致了这样的建议，即该过程可能在化石中蛋白质的非生物分解中起主要作用。3，4肽水解1 2345 6* 和蛋白质中氨基酸消旋化2，6的动力学和机理研究由于DKP形成和肽序列倒位而变得复杂。为了正确解释DKP可能形成的研究结果，需要对二肽-DKP系统有清楚的了解。
Cyclization and hydrolysis of aspartame were studied over a range of pH and temperatures by using an HPLC method which allows simultaneous analysis of the diastereomeric dipeptide and diketopiperazine products. The pH dependence of asparticacid and phenylalanine racemization rates in the dipeptide-diketopiperazine system resulting from aspartame decomposition was determined. On the basis of these studies a general scheme of relative epimerization rates of amino acids in diketopiperazines and in the various positions and ionic states of peptides is presented. This scheme is discussed in terms of the carbanion mechanism of amino acid racemization and found to be consistent with it. Racemization rates in the diketopiperazine were greater than those of all ionic forms of the free amino acids and dipeptides except for fully protonated free amino acids andprotonated terminal amino acids of peptides. In the neutral pH range the relative racemization rates in the DKP and dipeptides were DKP> amino terminal> carboxy terminal. Apparently contradictory results reported in the literature from dipeptide heating experiments were reanalyzed in terms of dipeptide-diketopiperazine-inverted dipeptide conversions. Viewed in this light, the literature is self-consistent and supports the generality of our scheme of relative racemizationrates and mechanistic conclusions.Intramolecular aminolysis of dipeptides and their de-rivatives to form cyclic dipeptides (diketopiperazines or DKPs) occurs readily in aqueous solution. 1, 2 Theubiquitous nature of this reaction has become apparent to workers in the fields of peptide chemistry and biogeo-chemistry. Rapid rates of internal aminolysis via DKP formation at the amino terminal of peptides has lead to the suggestion that this process mayplay a major role in the abiotic decomposition of proteins in fossils. 3, 4 Kinetic and mechanistic studies of peptide hydrolysis1 2345 6* and amino acid racemizationin proteins2, 6 have been complicated by DKP formation and peptide sequence inversion. In order to properly interpret results from studies wherein DKPs may form, a clear understanding of the dipeptide-DKP system is necessary.