tri(γ-glutamylcystainylglycinyl)trithioarsenite

• 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: tri(γ-glutamylcystainylglycinyl)trithioarsenite
• 英文别名: tris(L-glutathione) trithioarsenite；arsenic triglutathione；(2S)-2-amino-5-[[(2R)-3-bis[[(2R)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-3-(carboxymethylamino)-3-oxopropyl]sulfanyl]arsanylsulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₃₀H₄₈AsN₉O₁₈S₃
• 分子量: 993.88
• InChiKey: UXNWJLSRLNSHSI-QQCJEOGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.2
• 重原子数：
  61
• 可旋转键数：
  33
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  552
• 氢给体数：
  15
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  tri(γ-glutamylcystainylglycinyl)trithioarsenite 在 air 作用下， 以 水 为溶剂， 反应 168.0h， 以14%的产率得到L-谷胱甘肽 (氧化型)
  参考文献：
  名称：

  The Oxidation of Trialkyl Trithioarsenites, (RS)₃As, by Octasulfur/Triethylamine and Dioxygen

  摘要：

  Trialkyl trithioarsenites, (RS)(3) As, bearing terminal carboxy (COOH) or carboxylate (-COO-Na+) or zwitterionic (CH(NH3+)COO-) groups were studied for their ability to be oxidized by octasulfur, S-8, and by dioxygen. The carboxy-bearing trithioarsenites are not oxidized by S-8 to the corresponding As(V) esters, (RS)(3)As=S, probably because they cannot open the octasulfur ring, but they react with S-8 in the presence of triethylamine, which acts as an activator of S-8. The carboxylate-bearing trithioarsenites, however, do react under drastic conditions with S-8. In both cases colored insoluble solids were obtained which could not be characterized. The carboxy-bearing trithioarsenites are oxidized by air in a hydrocarbon chain-length depended manner, while the carboxylate-bearing trithioarsenites are not, if at all, oxidized by air to arsenic(III) oxide, As2O3, and disulfide, RSSR. The zwitterion-bearing tris(penicillamine), tris(cysteine), and tris(glutathione) trithioarsenites are air oxidized slower than their corresponding parent thiols and this may be of biochemical significance.

  DOI：

  10.1080/104265091001092
• 作为产物：
  描述：

  谷胱甘肽 在 sodium (meta)arsenite 作用下， 以 水 为溶剂， 生成 tri(γ-glutamylcystainylglycinyl)trithioarsenite
  参考文献：
  名称：

  通过选择性靶向白血病细胞优化砷治疗

  摘要：

  砷以简单形式的三氧化二砷目前已上市用于治疗急性早幼粒细胞白血病。由于砷的多方面作用机制，它在其他类型的白血病中也显示出希望，但因其对正常细胞的毒性作用而受到阻碍。这项研究的目的是确定是否可以设计和开发砷的肿瘤归巢肽复合物来战略性地靶向特定癌症。最终目标是减少所得砷治疗剂的剂量并减少副作用。在本文中，我们介绍了针对白血病的新型 As 肽复合物的合成、表征和稳定性研究。最稳定的复合物的体外生物学研究表明，其对白血病细胞的毒性比对人类血细胞的毒性高 1000 倍，表明有可能进展到体内研究。

  DOI：

  10.1021/acs.jmedchem.3c00676

文献信息

• Serves, Spyros V.; Charalambidis, Yiannis C.; Sotiropoulos, Demetrios N., Phosphorus, Sulfur and Silicon and the Related Elements, 1995, vol. 105, # 1-4, p. 109 - 116
  作者：Serves, Spyros V.、Charalambidis, Yiannis C.、Sotiropoulos, Demetrios N.、Ioannou, Panayiotis V.

  DOI：——

  日期：——
• In Vitro Effect of Arsenical Compounds on Glutathione-Related Enzymes
  作者：Salem Chouchane、Elizabeth T. Snow

  DOI：10.1021/tx000123x

  日期：2001.5.1

  The mechanism of arsenic toxicity is believed to be due to the ability of arsenite (As-III) to bind protein thiols. Glutathione (GSH) is the most abundant cellular thiol, and both GSH and GSH-related enzymes are important antioxidants that play an important role in the detoxification of arsenic and other carcinogens. The effect of arsenic on the activity of a variety of enzymes that use GSH has been determined using purified preparations of glutathione reductase (GR) from yeast and bovine glutathione peroxidase (GPx) and equine glutathione S-transferase (GST). The effect on enzyme activity of increasing concentrations (from 1 muM to 100 mM) of commercial sodium arsenite (As-III) and sodium arsenate (As-V) and a prepared arsenic(III)-glutathione complex [As-III(GS)(3)] and methylarsenous diiodide (CH3AsIII) has been examined. GR, GPx, and GST are not sensitive to As-V (IC50 > 50 mM), and none of the enzymes are inhibited or activated by physiologically relevant concentrations of As-III, As-III(GS)(3), or CH3-As-III, although CH3AsIII is the most potent inhibitor (0.3 mM < IC50 < 1.5 mM). GPx is the most sensitive to arsenic treatment and GST the least. Our results do not implicate a direct interaction of As with the glutathione-related enzymes, GR, GPx, and GST, in the mechanism of arsenic toxicity. CH3AsIII is the most effective inhibitor, but it is unclear whether this product of arsenic metabolism is produced at a sufficiently high concentration in critical target tissues to play a major role in either arsenic toxicity or carcinogenesis.
• The Oxidation of Trialkyl Trithioarsenites, (RS)₃As, by Octasulfur/Triethylamine and Dioxygen
  作者：Gerasimos M. Tsivgoulis、Theano C. Fotopoulou、Panayiotis V. Ioannou

  DOI：10.1080/104265091001092

  日期：2006.2

  Trialkyl trithioarsenites, (RS)(3) As, bearing terminal carboxy (COOH) or carboxylate (-COO-Na+) or zwitterionic (CH(NH3+)COO-) groups were studied for their ability to be oxidized by octasulfur, S-8, and by dioxygen. The carboxy-bearing trithioarsenites are not oxidized by S-8 to the corresponding As(V) esters, (RS)(3)As=S, probably because they cannot open the octasulfur ring, but they react with S-8 in the presence of triethylamine, which acts as an activator of S-8. The carboxylate-bearing trithioarsenites, however, do react under drastic conditions with S-8. In both cases colored insoluble solids were obtained which could not be characterized. The carboxy-bearing trithioarsenites are oxidized by air in a hydrocarbon chain-length depended manner, while the carboxylate-bearing trithioarsenites are not, if at all, oxidized by air to arsenic(III) oxide, As2O3, and disulfide, RSSR. The zwitterion-bearing tris(penicillamine), tris(cysteine), and tris(glutathione) trithioarsenites are air oxidized slower than their corresponding parent thiols and this may be of biochemical significance.
• Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells
  作者：Judith A. Carrall、Wilford Lie、Jacob M. Lambert、Hugh H. Harris、Barry Lai、Carolyn T. Dillon

  DOI：10.1021/acs.jmedchem.3c00676

  日期：2023.9.14

  Arsenic, in the simple form of arsenic trioxide, is currently marketed for the treatment of acute promyelocytic leukemia. Due to the multifaceted mechanisms of action of arsenic, it has also shown promise in other types of leukemias but is hindered by its toxic effects toward normal cells. This research has aimed to determine whether tumor-homing peptide complexes of arsenic can be designed and developed

  砷以简单形式的三氧化二砷目前已上市用于治疗急性早幼粒细胞白血病。由于砷的多方面作用机制，它在其他类型的白血病中也显示出希望，但因其对正常细胞的毒性作用而受到阻碍。这项研究的目的是确定是否可以设计和开发砷的肿瘤归巢肽复合物来战略性地靶向特定癌症。最终目标是减少所得砷治疗剂的剂量并减少副作用。在本文中，我们介绍了针对白血病的新型 As 肽复合物的合成、表征和稳定性研究。最稳定的复合物的体外生物学研究表明，其对白血病细胞的毒性比对人类血细胞的毒性高 1000 倍，表明有可能进展到体内研究。