9,10-dioxa-syn-(glutathionylmethyl,methyl)(methyl,methyl)bimane | 88859-65-8

• 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: 9,10-dioxa-syn-(glutathionylmethyl,methyl)(methyl,methyl)bimane
• 英文别名: bimane-S-glutathione；GS-bimane；L-GS-bimane；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-[(1,2,6-trimethyl-3,5-dioxopyrazolo[1,2-a]pyrazol-7-yl)methylsulfanyl]propan-2-yl]amino]-5-oxopentanoic acid
• CAS: 88859-65-8
• 化学式: C₂₀H₂₇N₅O₈S
• 分子量: 497.529
• InChiKey: KPJNKLWIESQKCG-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  225
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  谷胱甘肽 、 溴代双满 以 乙腈 为溶剂， 反应 0.33h， 生成 9,10-dioxa-syn-(glutathionylmethyl,methyl)(methyl,methyl)bimane
  参考文献：
  名称：

  吡咯烷定生物碱逆转录酶和莫诺他林的肝毒性比较研究。

  摘要：

  许多吡咯烷核苷生物碱（PAs）可能会导致动物和人类肝损伤。不同的肝毒性PA可以产生相似的肝毒性作用，但其毒性程度可能相差很大。Retrorsine（RTS）和Monocrotaline（MCT）共享相同的核心结构（retronecine）和相似的代谢激活途径。RTS和MCT均会造成肝损伤，但前者比后者更具肝毒性。酶动力学研究表明，RTS的Vmax / Km值是MCT的5.5倍。此外，在相同剂量下，RTS产生的吡咯-谷胱甘肽（GSH）缀合物和蛋白质共价结合水平更高。此外，RTS诱导了肝脏GSH的大量消耗，而MCT几乎没有。

  DOI：

  10.1021/acs.chemrestox.6b00260

文献信息

• Iterative synthetic strategies and gene deletant experiments enable the first identification of polysulfides in <i>Saccharomyces cerevisiae</i>
  作者：Lisa I. Pilkington、Rebecca C. Deed、Katie Parish-Virtue、Chien-Wei Huang、Michelle E. Walker、Vladimir Jiranek、David Barker、Bruno Fedrizzi

  DOI：10.1039/c9cc03020d

  日期：——

  Polysulfides, potential signalling molecules, were synthesised and then found and explored for the first time in yeast.

  聚硫化物，潜在的信号分子，首次在酵母中被合成、发现并探索。
• Bimanes. 17. (Haloalkyl)-1,5-diazabicyclo[3.3.O]octadienediones (halo-9,10-dioxabimanes): reactivity toward the tripeptide thiol, glutathione
  作者：Annette E. Radkowsky、Edward M. Kosower

  DOI：10.1021/ja00275a045

  日期：1986.7
• Plasmon-Resonance-Enhanced Absorption and Circular Dichroism
  作者：Itai Lieberman、Gabriel Shemer、Tcipi Fried、Edward M. Kosower、Gil Markovich

  DOI：10.1002/anie.200800231

  日期：2008.6.16
• Hepatic mercapturic acid formation: involvement of cytosolic cysteinylglycine S-conjugate dipeptidase activity
  作者：Claudio Jösch、Helmut Sies、Theodorus P.M Akerboom

  DOI：10.1016/s0006-2952(98)00065-3

  日期：1998.9

  The role of cysteinylglycine S-conjugate dipeptidases in the intrahepatic mercapturic acid pathway was investigated in rat liver. Subcellular compartmentation studies and liver perfusions were performed rising monochlorobimane and bimane S-conjugates as model compounds. The major parr (over 95%) of total hepatic cysteinylglycine S-conjugate dipeptidase activity was Located in the cytosol. Lower specific activity appeared in the canalicular plasma membrane fraction. Similar hepatic localization of dipeptidase activity was seen in the guinea pig. In intact rat liver perfused with monochlorobimane, the major products were the glutathione S-conjugate (mBSG) and the cysteinylglycine S-conjugate (mBCG) in bile. Minor amounts of the cysteine S-conjugate (mBCys) and the mercapturic acid (mBNAc) were formed, indicating a limitation in further metabolism of the dipeptide S-conjugate in the biliary space. However, when the dipeptide S-conjugate was offered to the sinusoidal space in liver perfusions, substantial uptake and conversion to mBNAc was observed, and only trace amounts of the infused dipeptide appeared in bile. The data suggest that cytosolic cysteinylglycine S-conjugate dipeptidase as identified here is involved in hepatic mercapturic acid formation from sinusoidal cysteinylglycine S-conjugates. This is especially of significance for species such as guinea pig and human, in which dipeptide S-conjugates are generated in the sinusoidal domain of the liver due to the presence of high gamma-glutamyltranspeptidase activity. (C) 1998 Elsevier Science Inc.
• Design and Synthesis of Highly Sensitive Fluorogenic Substrates for Glutathione S-Transferase and Application for Activity Imaging in Living Cells
  作者：Yuuta Fujikawa、Yasuteru Urano、Toru Komatsu、Kenjiro Hanaoka、Hirotatsu Kojima、Takuya Terai、Hideshi Inoue、Tetsuo Nagano

  DOI：10.1021/ja802423n

  日期：2008.11.5

  Here we report the development of fluorogenic substrates for glutathione S-transferase (GST), a multigene-family enzyme mainly involved in detoxification of endogenous and exogenous compounds, including drug metabolism. GST is often overexpressed in a variety of malignancies and is involved in the development of resistance to various anticancer drugs. Despite the medical significance of this enzyme, no practical fluorogenic substrates for fluorescence imaging of GST activity or for high-throughput screening of GST inhibitors are yet available. So, we set out to develop new fluorogenic substrates for GST. In preliminary studies, we found that 3,4-dinitrobenzanilide (NNBA) is a specific substrate for GST and established the mechanisms of its glutathionylation and denitration. Using these results as a basis for off/on control of fluorescence, we designed and synthesized new fluorogenic substrates, DNAFs, and a cell membrane-permeable variant, DNAT-Me. These fluorogenic substrates provide a dramatic fluorescence increase upon GST-catalyzed glutathionylation and have excellent kinetic parameters for the present purpose. We were able to detect nuclear localization of GSH/GST activity in HuCCT1 cell lines with the use of DNAT-Me. These results indicate that the newly developed fluorogenic substrates should be useful not only for high-throughput GST-inhibitor screening but also for studies on the mechanisms of drug resistance in cancer cells.