Important role of the 3-mercaptopropionamide moiety in glutathione: promoting effect on decomposition of the adduct of glutathione with the oxoammonium ion of TEMPO.
Important role of the 3-mercaptopropionamide moiety in glutathione: promoting effect on decomposition of the adduct of glutathione with the oxoammonium ion of TEMPO.
复制标题
谷胱甘肽中3-巯基丙酰胺部分的重要作用：促进谷胱甘肽与TEMPO的氧铵离子加合物分解的作用。
DOI：
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发表时间：
2005
影响因子：
3.6
通讯作者：
H. Ohmori
中科院分区：
文献类型：
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作者：
H. Maeda;Hong;Yuji Yamauchi;H. Ohmori
在谷胱甘肽（GSH）或半胱氨酸（Cys）的存在下，克里思在0.1M NaOH水溶液中的循环伏安法表明以下几点：（i）两种硫醇与克里思阳极产生的氧代铵离子1迅速形成加合物3。(ii)由GSH产生的3进入随后的反应，产生N-氧化物阴离子2-（还原的克里思）。(iii)由Cys产生的3在伏安法的时间尺度上保持完整。GSH的结构特征被认为有助于观察到的这种三肽的行为。可能的结构特征进行了评估，通过筛选各种硫醇的基础上，他们是否提供GSH样伏安结果。确定GSH中具有酰胺氢的3-巯基丙酰胺基团是GSH和Cys之间观察到的差异的原因。可能的功能是将3从GSH转化为5-亚氨基-1，2-氧硫杂环戊烷中间体，从而释放2-。代表GSH和Cys的模型硫醇与1的反应的产物分析为这一论点提供了支持，并表明GSH或Cys与1的反应将产生相应的二硫化物，无论是否形成五元环中间体。GSH的3-巯基丙酰胺部分的拟议功能可能提供有用的见解的分子设计的外源性巯基化合物作为新型药物治疗GSH耗尽相关的疾病。
Cyclic voltammetry of TEMPO in aqueous 0.1 M NaOH in the presence of glutathione (GSH) or cysteine (Cys) indicated the following points: (i) Both of the thiols rapidly formed adducts 3 with oxoammonium ion 1 anodically generated from TEMPO. (ii) 3 generated from GSH entered a succeeding reaction that generated N-oxide anion 2- (the reduced TEMPO). (iii) 3 produced from Cys remained intact over the time scale of voltammetry. A structural feature of GSH was considered to contribute to the observed behavior of this tripeptide. Possible structural features were evaluated by screening various thiols on the basis of whether they provided GSH-like voltammetric results. The 3-mercaptopropionamide group with an amide hydrogen in GSH was determined to be responsible for the observed difference between GSH and Cys. The likely function is to transform 3 from GSH into a 5-imino-1,2-oxathiolane intermediate, thereby releasing 2-. Product analysis for reactions of model thiols representing GSH and Cys with 1 provided support for this argument and suggested that the reaction of GSH or Cys with 1 would produce the corresponding disulfides, regardless of whether a five-membered ring intermediate was formed. The proposed function of the 3-mercaptopropionamide moiety of GSH may provide useful insight for the molecular design of exogenous thiol compounds as novel drugs for the treatment of GSH-depletion-related disorders.