(2S)-2-氨基-5-[[(2R)-2-氨基-3-(2-氯乙基硫基)丙酰]-(羧甲基)氨基]-5-氧代戊酸 | 75607-61-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2S)-2-氨基-5-[[(2R)-2-氨基-3-(2-氯乙基硫基)丙酰]-(羧甲基)氨基]-5-氧代戊酸
• 英文名称: S-(2-chloroethyl)glutathione
• 英文别名: (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(2-chloroethylsulfanyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 75607-61-3
• 化学式: C₁₂H₂₀ClN₃O₆S
• 分子量: 369.826
• InChiKey: KJTFFUUCBPMUPH-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  184
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  H-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 、 (2S)-2-氨基-5-[[(2R)-2-氨基-3-(2-氯乙基硫基)丙酰]-(羧甲基)氨基]-5-氧代戊酸 在 ammonium bicarbonate 作用下， 以 水 为溶剂， 反应 1.5h， 生成 、 、
  参考文献：
  名称：

  S-（2-氯乙基）谷胱甘肽将催产素烷基化，并通过串联质谱和Edman降解表征加合物。

  摘要：

  S-（2-氯乙基）谷胱甘肽（CEG）是由谷胱甘肽与1,2-二氯乙烷（DCE）共轭形成的烷基化剂，能够将DNA和蛋白质烷基化。作为鉴定特定蛋白质烷基化位点的前奏，通过CEG将肽催产素烷基化，并使用串联质谱法鉴定烷基化位点。发现还原的催产素的烷基化可导致单加合物，双加合物和三加合物，并且串联质谱法从（A-Cys-1）分离出了（S- [2-（Cys1）乙基]谷胱甘肽）催产素（单加合物Cys-1）。 （S- [2-（Cys1,6）乙基]谷胱甘肽）催产素（单加合物Cys-6）。对于（S- [2-（Cys1,6）乙基]谷胱甘肽）催产素（双加合物）和单酯，使用手动Edman降解消除了Tyr-2而不是Cys-1发生烷基化的可能性。 -加合物Cys-1。还鉴定了由Cys-6上的烷基化和通过Cys-1形成二硫键的单加合物同二聚体。氧化的催产素形成了两个次要的加合物，占反应混合物中催产素的不到5％。这些发现表明

  DOI：

  10.1021/tx00045a013
• 作为产物：
  描述：

  1-溴-2-氯乙烷 、 glutathione trisodium 以 甲醇 为溶剂， 生成 (2S)-2-氨基-5-[[(2R)-2-氨基-3-(2-氯乙基硫基)丙酰]-(羧甲基)氨基]-5-氧代戊酸
  参考文献：
  名称：

  Conjugation of Haloalkanes by Bacterial and Mammalian Glutathione Transferases:  Mono- and Vicinal Dihaloethanes

  摘要：

  Glutathione (GSH) transferases are generally involved in the detoxication of xenobiotic chemicals. However, conjugation can also activate compounds and result in DNA modification. Activation of 1,2-dihaloethanes (BrCH2CH2Br, BrCH2CH2Cl, and ClCH2CH2Cl) was investigated using two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial dichloromethane dehalogenase (DM11). Although the literature suggests that the bacterial dehalogenase does not catalyze reactions with CH3Cl, ClCH2CH2Cl, or CH3CHCl2, we found a higher enzyme efficiency for DM11 than for the mammalian GSH transferases in conjugating CH3Cl, CH3CH2Cl, and CH3CH2Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535 systems expressing each of these GSH transferases were used to determine mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases correlated with the mutagenicity determined in the reversion assays for the three 1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH] containing either F, Cl, or Br (as the leaving group) were tested for their abilities to induce revertants in S. typhimurium, and rates of hydrolysis were also determined. GSH transferases do not appear to be involved in the breakdown of the half-mustard intermediates. A halide order (Br > Cl) was observed for both GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from 1,2-dihaloethanes, with the single exception (both assays) of BrCH2CH2Cl reaction with DM11, which was unexpectedly high. The lack of substrate saturation seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases.

  DOI：

  10.1021/tx0100183

文献信息

• Alkylation of Oxytocin by S-(2-Chloroethyl)glutathione and Characterization of Adducts by Tandem Mass Spectrometry and Edman Degradation
  作者：John C. L. Erve、Max L. Deinzer、Donald J. Reed

  DOI：10.1021/tx00045a013

  日期：1995.4

  (DCE), is able to alkylate DNA and proteins. As a prelude to identification of specific protein alkylation sites, the peptide oxytocin was alkylated by CEG, and tandem mass spectrometry was used to identify the alkylation sites. It was found that mono-, bis-, and tris-adducts can result from alkylation of reduced oxytocin and that tandem mass spectrometry differentiated (S-[2-(Cys1)ethyl]glutathione)oxytocin

  S-（2-氯乙基）谷胱甘肽（CEG）是由谷胱甘肽与1,2-二氯乙烷（DCE）共轭形成的烷基化剂，能够将DNA和蛋白质烷基化。作为鉴定特定蛋白质烷基化位点的前奏，通过CEG将肽催产素烷基化，并使用串联质谱法鉴定烷基化位点。发现还原的催产素的烷基化可导致单加合物，双加合物和三加合物，并且串联质谱法从（A-Cys-1）分离出了（S- [2-（Cys1）乙基]谷胱甘肽）催产素（单加合物Cys-1）。 （S- [2-（Cys1,6）乙基]谷胱甘肽）催产素（单加合物Cys-6）。对于（S- [2-（Cys1,6）乙基]谷胱甘肽）催产素（双加合物）和单酯，使用手动Edman降解消除了Tyr-2而不是Cys-1发生烷基化的可能性。 -加合物Cys-1。还鉴定了由Cys-6上的烷基化和通过Cys-1形成二硫键的单加合物同二聚体。氧化的催产素形成了两个次要的加合物，占反应混合物中催产素的不到5％。这些发现表明
• Conjugation of Haloalkanes by Bacterial and Mammalian Glutathione Transferases:  Mono- and Vicinal Dihaloethanes
  作者：James B. Wheeler、Nina V. Stourman、Richard N. Armstrong、F. Peter Guengerich

  DOI：10.1021/tx0100183

  日期：2001.8.1

  Glutathione (GSH) transferases are generally involved in the detoxication of xenobiotic chemicals. However, conjugation can also activate compounds and result in DNA modification. Activation of 1,2-dihaloethanes (BrCH2CH2Br, BrCH2CH2Cl, and ClCH2CH2Cl) was investigated using two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial dichloromethane dehalogenase (DM11). Although the literature suggests that the bacterial dehalogenase does not catalyze reactions with CH3Cl, ClCH2CH2Cl, or CH3CHCl2, we found a higher enzyme efficiency for DM11 than for the mammalian GSH transferases in conjugating CH3Cl, CH3CH2Cl, and CH3CH2Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535 systems expressing each of these GSH transferases were used to determine mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases correlated with the mutagenicity determined in the reversion assays for the three 1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH] containing either F, Cl, or Br (as the leaving group) were tested for their abilities to induce revertants in S. typhimurium, and rates of hydrolysis were also determined. GSH transferases do not appear to be involved in the breakdown of the half-mustard intermediates. A halide order (Br > Cl) was observed for both GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from 1,2-dihaloethanes, with the single exception (both assays) of BrCH2CH2Cl reaction with DM11, which was unexpectedly high. The lack of substrate saturation seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases.