Fmoc-Cys(Acm)-Gly-OtBu | 186097-61-0

• 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
• 英文名称: Fmoc-Cys(Acm)-Gly-OtBu
• 英文别名: tert-butyl 2-[[(2R)-3-(acetamidomethylsulfanyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]amino]acetate
• CAS: 186097-61-0
• 化学式: C₂₇H₃₃N₃O₆S
• 分子量: 527.642
• InChiKey: LVNJCXGAZBEDFA-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.18
• 重原子数：
  37.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  122.83
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Fmoc-Cys(Acm)-Gly-OtBu 在 偶氮二甲酸二异丙酯 、 苯硫酚 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.25h， 生成 H-MeCys(Acm)-Gly-OtBu
  参考文献：
  名称：

  Peptidomimetic Glutathione Analogues as Novel γGT Stable GST Inhibitors

  摘要：

  Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper., we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards gamma -glutamyl-transpeptidase (gamma GT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the gamma -glutamyl-cysteine amide bond greatly improved stability towards GT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00269-3
• 作为产物：
  描述：

  甘氨酸叔丁酯盐酸盐 、 2'-O-triflyl-3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-ara-adenosine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 达卡巴嗪 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 以98%的产率得到Fmoc-Cys(Acm)-Gly-OtBu
  参考文献：
  名称：

  Peptidomimetic Glutathione Analogues as Novel γGT Stable GST Inhibitors

  摘要：

  Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper., we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards gamma -glutamyl-transpeptidase (gamma GT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the gamma -glutamyl-cysteine amide bond greatly improved stability towards GT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00269-3

文献信息

• Synthesis and Activity of the Glutathione Analogue γ-(L-γ-Oxaglutamyl)-L-cysteinyl-glycine
  作者：Anna Calcagni、Silvestro Duprè、Gino Lucente、Grazia Luisi、Francesco Pinnen、Domenico Rossi、Alessandra Spirito

  DOI：10.1002/ardp.19963291105

  日期：——

  An efficient synthesis of the backbone modified glutathione analogue γ‐(L‐γ‐oxaglutamyl)‐L‐cysteinyl‐glycine (7), characterized by the presence of an urethane O‐CO‐NH linkage replacing the γ‐glutamylic CH2CO‐NH fragment is described. The new analogue has been fully characterized by 1H‐ and 13C‐NMR, and FAB‐MS. Compound 7 was tested for inhibition of γ‐glutamyl‐transferase activity and was found to

  骨架修饰的谷胱甘肽类似物 γ- (L - γ - oxaglutamyl) -L - 半胱氨酰 - 甘氨酸 (7) 的有效合成，其特征在于存在氨基甲酸酯 O - CO - NH 键取代 γ - 谷氨酰 CH2CO - NH 片段被描述。新的类似物已通过 1H- 和 13C-NMR 以及 FAB-MS 进行了全面表征。测试了化合物 7 对 γ-谷氨酰转移酶活性的抑制作用，发现它是猪肾 γ-谷氨酰转移酶 (EC 2.3.2.2) 的非竞争性抑制剂。