(4Z,7Z,10Z,13Z,15E,17S,19Z)-17-hydroperoxydocosa-4,7,10,13,15,19-hexaenoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (4Z,7Z,10Z,13Z,15E,17S,19Z)-17-hydroperoxydocosa-4,7,10,13,15,19-hexaenoate
• 化学式: C22H31O4-
• 分子量: 359.5
• InChiKey: BNHQALRBDJVUQB-YTQNUIGOSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate 、 氧气 生成 (4Z,7Z,10Z,13Z,15E,17S,19Z)-17-hydroperoxydocosa-4,7,10,13,15,19-hexaenoate
  参考文献：
  名称：

  铜绿假单胞菌细菌脂加氧酶磷脂加氧酶活性的结构和功能基础

  摘要：

  铜绿假单胞菌（Pseudomonas aeruginosa）表达一种分泌的LOX同工型（PA-LOX，LoxA），其能够将多聚脂肪酸氧化为氢过氧衍生物。在这里，我们报告这种酶在大肠杆菌中的高水平表达及其结构和功能表征。重组PA-LOX将包括二十碳五烯酸和二十二碳六烯酸的多烯脂肪酸氧化为相应的（n-6）S-氢过氧衍生物。该反应涉及从n-8双烯丙基亚甲基中提取原S-氢。PA-LOX缺乏主要的白三烯合酶活性，但可转化5 S -HETE和5 S，6 R / S-DiHETE抗炎和促分解脂蛋白。它也表现出磷脂加氧酶活性，这是由来自不同磷脂亚种的氧化产物的特定模式的形成所表明的。多个诱变研究表明，PA-LOX不遵循解释哺乳动物LOXs反应特异性的经典概念。PA-LOX的晶体结构解析度高达1.48Å，其多肽链折叠成单个结构域。底物结合袋由两个脂肪酸结合子腔和大厅组成。Subcavity-1包含催化性非血

  DOI：

  10.1016/j.bbalip.2016.08.002

文献信息

• 15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-lipoxygenase-2 in biosynthesis of resolvin D5
  作者：Steven C. Perry、Chakrapani Kalyanaraman、Benjamin E. Tourdot、William S. Conrad、Oluwayomi Akinkugbe、John Cody Freedman、Michael Holinstat、Matthew P. Jacobson、Theodore R. Holman

  DOI：10.1194/jlr.ra120000777

  日期：2020.7

  (diHDHA) and 7S,17S-diHDHA [resolvin D5 (RvD5)] have been found in macrophages and infectious inflammatory exudates and are believed to function as specialized pro-resolving mediators (SPMs). Their biosynthesis is thought to proceed through sequential oxidations of DHA by lipoxygenase (LOX) enzymes, specifically, by human 5-LOX (h5-LOX) first to 7(S)-hydroxy-4Z,8E,10Z,13Z,16Z,19Z-DHA (7S-HDHA), followed

  已在巨噬细胞和感染性炎症渗出液中发现了两种 oxylipins 7S,14S-二羟基二十二碳六烯酸 (diHDHA) 和 7S,17S-diHDHA [resolvin D5 (RvD5)]，并被认为是专门的促分解介质 (SPM)。它们的生物合成被认为是通过脂氧合酶 (LOX) 对 DHA 的顺序氧化进行的，具体来说，首先是人 5-LOX (h5-LOX) 到 7(S)-羟基-4Z,8E,10Z,13Z,16Z,19Z -DHA (7S-HDHA)，然后是人血小板 12-LOX (h12-LOX) 形成 7(S),14(S)-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-DHA (7S, 14S-diHDHA) 或人网织红细胞 15-LOX-1 (h15-LOX-1) 形成 RvD5。在这项工作中，我们确定了 7(S)-hydroperoxy-4Z,8E,10Z,13Z,16Z
• Biogenic Synthesis, Purification, and Chemical Characterization of Anti-inflammatory Resolvins Derived from Docosapentaenoic Acid (DPAn-6)
  作者：Bindi Dangi、Marcus Obeng、Julie M. Nauroth、Mah Teymourlouei、Micah Needham、Krishna Raman、Linda M. Arterburn

  DOI：10.1074/jbc.m809014200

  日期：2009.5

  Enzymatically oxygenated derivatives of the omega-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197-1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677-14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain polyunsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S (TM) oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)-dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins.