5(S)-hydroperoxy-18(R)-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate

• 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: 5(S)-hydroperoxy-18(R)-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate
• 英文别名: (5S,6E,8Z,11Z,14Z,16E,18R)-5-hydroperoxy-18-hydroxyicosa-6,8,11,14,16-pentaenoate
• 化学式: C20H29O5-
• 分子量: 349.4
• InChiKey: JIOJPWROWDJRKM-NNQKPOSRSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5(S)-hydroperoxy-18(R)-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate 生成 5(S),6(S)-epoxy-18(R)-hydroxy-(7E,9E,11Z,14Z,16E)-icosapentaenoate 、 水
  参考文献：
  名称：

  Resolvin E2: Identification and Anti-Inflammatory Actions: Pivotal Role of Human 5-Lipoxygenase in Resolvin E Series Biosynthesis

  摘要：

  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.

  DOI：

  10.1016/j.chembiol.2006.09.011
• 作为产物：
  描述：

  18R-hydroxy-eicosapentaenoate 、 氧气 生成 5(S)-hydroperoxy-18(R)-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate
  参考文献：
  名称：

  Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation

  摘要：

  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.

  DOI：

  10.1172/jci42545

文献信息

• Resolvin E2 Formation and Impact in Inflammation Resolution
  作者：Sungwhan F. Oh、Maria Dona、Gabrielle Fredman、Sriram Krishnamoorthy、Daniel Irimia、Charles N. Serhan

  DOI：10.4049/jimmunol.1103652

  日期：2012.5.1

  Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1–10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein–coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (Kd 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein–coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.

  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。