12-氢过氧基二十碳-5,8,10,14-四烯酸 | 67675-13-2

• 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: 12-氢过氧基二十碳-5,8,10,14-四烯酸
• 英文名称: 12-hydroperoxyeicosa-5,8,10,14-tetraenoic acid
• 英文别名: 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid；Arachidonic acid omega-9 hydroperoxide；12-hydroperoxyicosa-5,8,10,14-tetraenoic acid
• CAS: 67675-13-2
• 化学式: C₂₀H₃₂O₄
• 分子量: 336.472
• InChiKey: ZIOZYRSDNLNNNJ-UHFFFAOYSA-N

物化性质

• 沸点：
  518.0±50.0 °C(Predicted)
• 密度：
  1.013±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  12-氢过氧基二十碳-5,8,10,14-四烯酸 在 吡啶 、 乙酸酐 作用下， 生成 (5Z,8Z,10E,14Z)-12-氧代-5,8,10,14-二十碳四烯酸
  参考文献：
  名称：

  Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes

  摘要：

  Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of increasing interest to researchers due to their involvement in different inflammatory responses in the cell. Oxo-lipids are unique because they contain electrophilic sites that can potentially form covalent bonds through a Michael addition mechanism with nucleophilic residues in protein active sites and thus increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15-lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE exhibited the highest potency against h12-LOX, with an IC50 = 1 +/- 0.1 mu M and was highly selective. Steady state inhibition kinetic experiments determined 15-oxo-ETE to be a mixed inhibitor against h12-LOX, with a K-ic value of 0.087 +/- 0.008 mu M and a K-iu value of 2.10 +/- 0.8 mu M. Time-dependent studies demonstrated irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration of 12-oxo-ETE required (K-i = 36.8 +/- 13.2 mu M) and the time frame (k(2) = 0.0019 +/- 0.00032 s(-1)) were not biologically relevant. These data are the first observations that oxo-lipids can inhibit LOX isozymes and may be another mechanism in which LOX products regulate LOX activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.05.025
• 作为产物：
  描述：

  花生四烯酸 在 human platelet 12-lipoxygenase 作用下， 以 aq. buffer 为溶剂， 生成 12-氢过氧基二十碳-5,8,10,14-四烯酸
  参考文献：
  名称：

  Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes

  摘要：

  Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of increasing interest to researchers due to their involvement in different inflammatory responses in the cell. Oxo-lipids are unique because they contain electrophilic sites that can potentially form covalent bonds through a Michael addition mechanism with nucleophilic residues in protein active sites and thus increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15-lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE exhibited the highest potency against h12-LOX, with an IC50 = 1 +/- 0.1 mu M and was highly selective. Steady state inhibition kinetic experiments determined 15-oxo-ETE to be a mixed inhibitor against h12-LOX, with a K-ic value of 0.087 +/- 0.008 mu M and a K-iu value of 2.10 +/- 0.8 mu M. Time-dependent studies demonstrated irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration of 12-oxo-ETE required (K-i = 36.8 +/- 13.2 mu M) and the time frame (k(2) = 0.0019 +/- 0.00032 s(-1)) were not biologically relevant. These data are the first observations that oxo-lipids can inhibit LOX isozymes and may be another mechanism in which LOX products regulate LOX activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.05.025

文献信息

• Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes
  作者：Michelle M. Armstrong、Giovanni Diaz、Victor Kenyon、Theodore R. Holman

  DOI：10.1016/j.bmc.2014.05.025

  日期：2014.8

  Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of increasing interest to researchers due to their involvement in different inflammatory responses in the cell. Oxo-lipids are unique because they contain electrophilic sites that can potentially form covalent bonds through a Michael addition mechanism with nucleophilic residues in protein active sites and thus increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15-lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE exhibited the highest potency against h12-LOX, with an IC50 = 1 +/- 0.1 mu M and was highly selective. Steady state inhibition kinetic experiments determined 15-oxo-ETE to be a mixed inhibitor against h12-LOX, with a K-ic value of 0.087 +/- 0.008 mu M and a K-iu value of 2.10 +/- 0.8 mu M. Time-dependent studies demonstrated irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration of 12-oxo-ETE required (K-i = 36.8 +/- 13.2 mu M) and the time frame (k(2) = 0.0019 +/- 0.00032 s(-1)) were not biologically relevant. These data are the first observations that oxo-lipids can inhibit LOX isozymes and may be another mechanism in which LOX products regulate LOX activity. (C) 2014 Elsevier Ltd. All rights reserved.