Savige W E, Fontana A
Int J Pept Protein Res. 1980 Feb;15(2):102-12.
The reaction of L-3a-hydroxy-1,2,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (Hpi) with methanethiol, ethanethiol, mercaptoethanol or 3-mercaptopropionic acid in warm aqueous acetic acid gives the corresponding 2-thioether derivatives of tryptophan in 50--80% yield (based on Hpi). Better yields may be obtained in 25% trifluoroacetic acid at room temperature. Cysteine reacts with Hpi to give the double amino acid 2-(L-3-alanylthio)-L-tryptophan (tryptathionine), which is a constituent of the highly poisonous cyclopeptides of Amanita phalloides, such as phalloidin. Reaction of a moderate excess of Hpi with cysteine-SH groups of a tripeptide (glutathione) and a protein (reduced ribonuclease) has also been effected, giving the respective S-tryptophanylated peptide or protein. In both cases, reaction occurred specifically with the -SH groups of cysteine and virtually quantitative covalent binding of tryptophan was verified. The extent of the reaction is easily quantitated by spectrophotometry or by amino acid analysis of the content of oxindolylalanine in the hydrolysate with hot 3-N p-toluenesulfonic acid of the S-tryptophanylated peptide or protein. The reaction should be useful in the field of peptide synthesis, providing a simple method for establishing a cross-link between tryptophan and cysteine, as a basic step in the chemical synthesis of toxic peptides of Amanita phalloides.
L-3a-羟基-1,2,3a,8,8a-六氢吡咯并[2,3-b]吲哚-2-羧酸（Hpi）与甲硫醇、乙硫醇、巯基乙醇或3-巯基丙酸在温热的乙酸水溶液中反应，以50%至80%的产率（基于Hpi）生成相应的色氨酸2-硫醚衍生物。在室温下于25%的三氟乙酸中可获得更高的产率。半胱氨酸与Hpi反应生成双氨基酸2-(L-3-丙氨硫基)-L-色氨酸（色氨硫醚），它是毒蝇伞剧毒环肽（如鬼笔环肽）的组成成分。适量过量的Hpi与三肽（谷胱甘肽）和蛋白质（还原核糖核酸酶）的半胱氨酸-SH基团也发生了反应，分别生成了S-色氨酸化的肽或蛋白质。在这两种情况下，反应都特异性地发生在半胱氨酸的-SH基团上，并且证实色氨酸几乎发生了定量的共价结合。通过分光光度法或对S-色氨酸化肽或蛋白质用热的3-N对甲苯磺酸水解产物中羟吲哚丙氨酸含量进行氨基酸分析，可轻松定量反应程度。该反应在肽合成领域应会有用，为在色氨酸和半胱氨酸之间建立交联提供了一种简单方法，这是毒蝇伞毒性肽化学合成中的一个基本步骤。
