(5S,6E,8Z,11Z,14Z,16E,18R)-5,18-dihydroxyicosa-6,8,11,14,16-pentaenoate

• 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: (5S,6E,8Z,11Z,14Z,16E,18R)-5,18-dihydroxyicosa-6,8,11,14,16-pentaenoate
• 化学式: C20H29O4-
• 分子量: 333.4
• InChiKey: KPRHYAOSTOHNQA-NNQKPOSRSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5(S)-hydroperoxy-18(R)-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate 、 AH₂ 生成 A 、 水 、 (5S,6E,8Z,11Z,14Z,16E,18R)-5,18-dihydroxyicosa-6,8,11,14,16-pentaenoate
  参考文献：
  名称：

  Resolvin E2 Formation and Impact in Inflammation Resolution

  摘要：

  急性炎症及其解决过程对于组织保护和稳态至关重要。在这种情况下，从多不饱和脂肪酸中衍生出的专门的促解决介质具有重要意义。在这项研究中，我们报告了自限性小鼠腹膜炎在启动和解决阶段都内源性产生的来自二十碳五烯酸的解决素E2（RvE2）。 RvE2（1-10 nM）具有强大的白细胞定向作用，包括：1）调节人类中性粒细胞的趋化作用；和2）增强吞噬作用和抗炎细胞因子的产生。这些作用似乎是通过白细胞G蛋白偶联受体介导的，因为标记的RvE2的制备提供了放射性标记的RvE2与中性粒细胞的特异性结合的直接证据（Kd 24.7±10.1 nM），并评估了解决素E1对重组G蛋白偶联受体的激活。除了小鼠的炎症环境外，RvE2还在健康人体内的血浆中被鉴定出来。 RvE2迅速降低了全血中人类白细胞整合素的表面表达，并减弱了对激活血小板因子的反应。这些结果表明，RvE2可以在先天性炎症反应的启动和解决过程中刺激宿主保护作用。

  DOI：

  10.4049/jimmunol.1103652

文献信息

• Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation
  作者：Sungwhan F. Oh、Padmini S. Pillai、Antonio Recchiuti、Rong Yang、Charles N. Serhan

  DOI：10.1172/jci42545

  日期：2011.2.1

  E-series resolvins are antiinflammatory and pro-resolving lipid mediators derived from the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that actively clear inflammation to promote tissue homeostasis. Aspirin, in addition to exerting antithrombotic actions, also triggers the biosynthesis of these specialized pro-resolving mediators. Here, we used metabolomic profiling to investigate the biosynthesis of E-series resolvins with specific chiral chemistry in serum from human subjects and present evidence for new 18S series resolvins. Aspirin increased endogenous formation of 18S-hydroxyeicosapentaenoate (18S-HEPE) compared with 18R-HEPE, a known resolvin precursor. Human recombinant 5-lipoxygenase used both enantiomers as substrates, and recombinant LTA(4) hydrolase (LTA4H) converted chiral 5S(6)-epoxide-containing intermediates to resolvin El and 18S-resolvin El (RvE1 and 18S-RvE1, respectively). 18S-RvE1 bound to the leukocyte GPCRs ChemR23 and BLT1 with increased affinity and potency compared with the R-epimer, but was more rapidly inactivated than RvE1 by dehydrogenase. Like RvE1, 18S-RvE1 enhanced macrophage phagocytosis of zymosan, E. coli, and apoptotic neutrophils and reduced both neutrophil infiltration and proinflammatory cytokines in murine peritonitis. These results demonstrate two parallel stereospecific pathways in the biosynthesis of E-series resolvins, 18R- and 18S-, which are antiinflammatory, pro-resolving, and non-phlogistic and may contribute to the beneficial actions of aspirin and omega-3 polyunsaturated fatty acids.
• Resolvin E2: Identification and Anti-Inflammatory Actions: Pivotal Role of Human 5-Lipoxygenase in Resolvin E Series Biosynthesis
  作者：Eric Tjonahen、Sungwhan F. Oh、Jeffrey Siegelman、Siva Elangovan、Katherine B. Percarpio、Song Hong、Makoto Arita、Charles N. Serhan

  DOI：10.1016/j.chembiol.2006.09.011

  日期：2006.11

  The family of resolvins consists of omega-3 fatty acid-derived mediators, including E series resolvins generated from eicosapentaenoic acid (EPA), and carry potent anti-inflammatory properties. Here, we report the isolation, identification, and bioactions of resolvin E2 (RvE2), which is 5S,18-dihydroxy-eicosapentaenoic acid. RvE2 stopped zymosan-induced polymorphonuclear (PMN) leukocyte infiltration and displayed potent anti-inflammatory properties in murine peritonitis. We also demonstrate that human recombinant 5-lipoxygenase generates RvE2 from a common precursor of E series resolvins, namely, 18-hydroxyeicosapentaenoate (18-HEPE). Furthermore, the initial 5-hydroperoxide intermediate was also converted to a 5(6)-epoxide intermediate in RvE1 formation. These results demonstrate that RvE2, together with RvE1, may contribute to the beneficial actions of omega-3 fatty acids in human diseases. Moreover, they indicate that the 5-lipoxygenase in human leukocytes is a pivotal enzyme that can produce both pro- and anti-inflammatory chemical mediators.