8-异前列腺素A2 | 474391-66-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 8-异前列腺素A2
• 英文名称: 8-iso-prostaglandin A₂
• 英文别名: 8-iso-prostaglandin A2；(Z)-7-[(1S,2S)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopent-3-en-1-yl]hept-5-enoic acid
• CAS: 474391-66-7
• 化学式: C₂₀H₃₀O₄
• 分子量: 334.456
• InChiKey: MYHXHCUNDDAEOZ-UKUWKSPLSA-N

物化性质

• 沸点：
  515.3±50.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：>75mg/mL； DMSO：>50mg/mL；乙醇：>100mg/mL； PBS pH 7.2：>2.4 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 8-异前列腺素A2 在 human glutathione transferase A₄-4 作用下， 以 phosphate buffer 、 乙醇 为溶剂， 生成 (Z)-7-[(1S,2R)-3-[(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-2-((E)-(S)-3-hydroxy-oct-1-enyl)-5-oxo-cyclopentyl]-hept-5-enoic acid
  参考文献：
  名称：

  The Cyclopentenone Product of Lipid Peroxidation, 15-A_2t-Isoprostane (8-Isoprostaglandin A₂), Is Efficiently Conjugated with Glutathione by Human and Rat Glutathione Transferase A4-4

  摘要：

  Glutathione transferases (GSTs) are a large family of enzymes that can be divided into different classes based on structure. There has been considerable interest in the ability of GSTs to conjugate and inactivate endogenously derived reactive lipid peroxidation products that contain alpha,beta-unsaturated carbonyl moieties such as 4-hydroxyalkenals. One enzyme with prominent activity toward these substrates is human GST A4-4. Recently, we described a novel series of compounds termed A(2)/J(2)-isoprostanes (IsoPs) that are formed endogenously in humans from the free radical-initiated peroxidation of arachidonic acid. These compounds contain (alpha,beta-unsaturated carbonyl groups and have structures similar to cyclooxygenase-derived PGA(2) and PGJ(2). Because of their chemical reactivity, these compounds may mediate tissue injury associated with oxidant stress. Herein, we report that the A-ring IsoP 15-A(2t)-ISOP (8-iso-PGA(2)) is efficiently conjugated to glutathione (GSH) by human GST A4-4 with a k(cat)/K-m value of > 200 S-1 mM(-1). The k(cat)/K-m value for conjugation of 15-A(2t)-IsoP by the homologous rat GST A4-4 is >2000 s(-1) mM-1. Similar high enzyme activities were observed when PGA2 was used as a substrate. In contrast, the human GSTs A1-1, M1-1, M2-2, P1-1, and T1-1 and rat GST T2-2 did not significantly metabolize 15-A(2t)-IsoP. These studies have therefore defined a potentially important route by which cyclopentenone IsoPs are metabolized that may serve as a mechanism for the inactivation of these highly reactive compounds.

  DOI：

  10.1021/tx020027r