(11S)-11-羟基二十碳-5,8,12,14-四烯酸 | 54886-50-9

• 物质功能分类: 生物化工 - 生化试剂
• 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: (11S)-11-羟基二十碳-5,8,12,14-四烯酸
• 英文名称: (11S)-hydroxyeicosatetraenoic acid
• 英文别名: 11S-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid；11(S)-HETE；(5Z,8Z,11S,12E,14Z)-11-hydroxyicosa-5,8,12,14-tetraenoic acid
• CAS: 54886-50-9
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: GCZRCCHPLVMMJE-YZGNWCGPSA-N

物化性质

• 溶解度：
  0.1 M Na2CO3：2 mg/mL； DMF：可混溶； DMSO：可混溶；乙醇：可混溶； PBS pH 7.2：0.8 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  F,Xi
• 危险类别码：
  R36/37/38,R11
• 危险品运输编号：
  UN 1170 3/PG 2
• 海关编码：
  2918199090
• 安全说明：
  S16,S26,S36
• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

rat中性粒细胞PMNL合成11-HETE已被报道，但其立体化学尚未明确。

反应信息

• 作为反应物：
  描述：

  (11S)-11-羟基二十碳-5,8,12,14-四烯酸 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Production of Hydroxy Unsaturated Fatty Acids Using Crude Lipoxygenase Obtained from Infected Rice Plants

  摘要：

  为了探索从感染的水稻植物中获得的脂氧化酶（LOX）的氧化模式，通过LOX和氧气处理了典型的不饱和脂肪酸（3—8）。观察到在异源ω-6（4和5）和ω-3（7和8）系列的不饱和脂肪酸中，主要在ω-10和ω-6位发生氧化。而在内源性脂肪酸（3和6）的情况下，ω-6位的氧化占主导地位。通过用NaBH4还原氧化产物获得的所有烯丙醇均具有S构型。

  DOI：

  10.1246/bcsj.69.1663
• 作为产物：
  描述：

  花生四烯酸 在 sodium tetrahydroborate 、 Tris-HCl buffer 、 lipoxygenase 、 borate buffer 作用下， 生成 (11S)-11-羟基二十碳-5,8,12,14-四烯酸
  参考文献：
  名称：

  Production of Hydroxy Unsaturated Fatty Acids Using Crude Lipoxygenase Obtained from Infected Rice Plants

  摘要：

  为了探索从感染的水稻植物中获得的脂氧化酶（LOX）的氧化模式，通过LOX和氧气处理了典型的不饱和脂肪酸（3—8）。观察到在异源ω-6（4和5）和ω-3（7和8）系列的不饱和脂肪酸中，主要在ω-10和ω-6位发生氧化。而在内源性脂肪酸（3和6）的情况下，ω-6位的氧化占主导地位。通过用NaBH4还原氧化产物获得的所有烯丙醇均具有S构型。

  DOI：

  10.1246/bcsj.69.1663

文献信息

• Improved Sensitivity Mass Spectrometric Detection of Eicosanoids by Charge Reversal Derivatization
  作者：James G. Bollinger、Wallace Thompson、Ying Lai、Rob C. Oslund、Teal S. Hallstrand、Martin Sadilek、Frantisek Turecek、Michael H. Gelb

  DOI：10.1021/ac100720p

  日期：2010.8.15

  eicosanoids to a cationic AMPP amide improves sensitivity of detection by 10- to 20-fold compared to negative mode electrospray ionization detection of underivatized analytes. This charge reversal derivatization allows detection of cations rather than anions in the electrospray ionization mass spectrometer, which enhances sensitivity. Another factor is that AMPP amides undergo considerable collision-induced dissociation

  液相色谱-电喷雾电离-串联质谱联用 (LC-ESI-MS/MS) 是一种分析多不饱和脂肪酸（包括类二十烷酸）含氧代谢物的强大方法。这里我们描述了一种新的衍生化试剂N的合成-(4-氨基甲基苯基)吡啶鎓 (AMPP)，可通过酰胺键以定量产率与类二十烷酸偶联。与未衍生化分析物的负模式电喷雾电离检测相比，将类二十烷酸的羧酸转化为阳离子 AMPP 酰胺可将检测灵敏度提高 10 到 20 倍。这种电荷反转衍生允许在电喷雾电离质谱仪中检测阳离子而不是阴离子，从而提高灵敏度。另一个因素是 AMPP 酰胺在分析物部分而不是仅在阳离子标签部分发生相当大的碰撞诱导解离，这使得同量异位衍生物可以通过串联质谱法进行区分，这进一步提高了灵敏度和特异性。这种简单的衍生方法允许前列腺素，2、白三烯B 4、羟基二十碳四烯酸异构体和花生四烯酸在复杂生物样品中定量，定量限在200-900 fg范围内。可以预期，AMPP 衍生化
• Reagent and method for detection of carboxylic acids by mass spectrometry
  申请人：Gelb Michael H.

  公开号：US09045421B2

  公开（公告）日：2015-06-02

  Method and reagent for converting a carboxylic acid to a positively charge amide are described. The method and reagent facilitate positive ion mass spectral analysis of carboxylic acids. The method includes reacting a carboxylic acid with a compound having formula I: wherein A and B are aromatic rings, ring A includes a quaternized nitrogen and has n additional ring atoms, each additional ring atom optionally substituted with an RA group, and n is an integer from 4 to 10, and ring B includes a carbon atom and has m additional ring atoms, each additional ring atom optionally substituted with an RB group, and m is an integer from 4 to 10. The compound includes at least one RA or RB group, and the at least one RA and RB group is -L-N(Z)H; and X− is a counterion.

  描述了将羧酸转化为带正电荷的酰胺的方法和试剂。该方法和试剂有助于对羧酸进行正离子质谱分析。该方法包括将羧酸与具有以下式I的化合物反应：其中A和B为芳香环，环A包括一个季铵氮，并且具有n个额外的环原子，每个额外的环原子可选择地被RA基取代，n为4至10之间的整数，环B包括一个碳原子，并具有m个额外的环原子，每个额外的环原子可选择地被RB基取代，m为4至10之间的整数。该化合物包括至少一个RA或RB基，至少一个RA和RB基为-L-N(Z)H；X-为一个对离子。
• Physcomitrella patens has lipoxygenases for both eicosanoid and octadecanoid pathways
  作者：Aldwin Anterola、Cornelia Göbel、Ellen Hornung、George Sellhorn、Ivo Feussner、Howard Grimes

  DOI：10.1016/j.phytochem.2008.11.012

  日期：2009.1

  Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 alpha-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering plants. To identify the fatty acid substrates used by moss lipoxygenases, eight lipoxygenase genes from Physcomitrella patens were heterologously expressed in Escherichia coli, and then analyzed for lipoxygenase activity using linoleic, alpha-linolenic and arachidonic acids as substrates. Among the eight moss lipoxygenases, only seven were found to be enzymatically active in vitro, two of which selectively used arachidonic acid as the substrate, while the other five preferred alpha-linolenic acid. Based on enzyme assays using a Clark-type oxygen electrode, all of the active lipoxygenases had an optimum pH at 7.0, except for one with highest activity at pH 5.0. HPLC analyses indicated that the two arachidonic acid lipoxygenases form (12S)-hydroperoxy eicosatetraenoic acid as the main product, while the other five lipoxygenases produce mainly (13S)-hydroperoxy octadecatrienoic acid from alpha-linolenic acid. These results suggest that mosses may have both C20 and C18 based oxylipin pathways. Published by Elsevier Ltd.
• Crystal Structure of a Lipoxygenase in Complex with Substrate
  作者：David B. Neau、Gunes Bender、William E. Boeglin、Sue G. Bartlett、Alan R. Brash、Marcia E. Newcomer

  DOI：10.1074/jbc.m114.599662

  日期：2014.11

  Background: Lipoxygenases (LOX) catalyze the oxygenation of polyunsaturated fatty acids but generate distinct products from a common substrate. Results: We report the first structure of a LOX-substrate complex. Conclusion: The structure provides a context for understanding product specificity in enzymes that metabolize arachidonic acid. Significance: With roles in the production of potent lipid mediators, LOX are targets for drug design.Lipoxygenases (LOX) play critical roles in mammalian biology in the generation of potent lipid mediators of the inflammatory response; consequently, they are targets for the development of isoform-specific inhibitors. The regio- and stereo-specificity of the oxygenation of polyunsaturated fatty acids by the enzymes is understood in terms of the chemistry, but structural observation of the enzyme-substrate interactions is lacking. Although several LOX crystal structures are available, heretofore the rapid oxygenation of bound substrate has precluded capture of the enzyme-substrate complex, leaving a gap between chemical and structural insights. In this report, we describe the 2.0 angstrom resolution structure of 8R-LOX in complex with arachidonic acid obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of arachidonic acid in a catalytically competent conformation. Accompanying experimental work supports a model in which both substrate tethering and cavity depth contribute to positioning the appropriate carbon at the catalytic machinery.
• Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2
  作者：Surafel Mulugeta、Takashi Suzuki、Noemi Tejera Hernandez、Markus Griesser、William E. Boeglin、Claus Schneider

  DOI：10.1194/jlr.m001719

  日期：2010.3

  Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy-6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate crossover of the 5-LOX and COX-2 pathways as an additional bio-synthetic route.-Mulugeta, S., T. Suzuki, N. T. Hernandez, M. Griesser, W. E. Boeglin, and C. Schneider. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2. J. Lipid Res. 2010. 51: 575-585.