月桂酰溶血磷酰脂 | 20559-18-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 中文名称: 月桂酰溶血磷酰脂
• 中文别名: L-A-溶血磷酰脂胆碱；1-月桂酰溶血卵磷酯；1-月桂基-2-羟基-sn-甘油-3-磷酸胆碱；1月桂酰基-2-羟基-SN-甘油-3-磷酸胆碱；(R)-3-(十二烷酰氧基)-2-羟丙基(2-(三甲基铵)乙基)磷酸酯；1-月桂基-2-羟基-SN-甘油-3-磷酸胆碱
• 英文名称: LPC (12:0)
• 英文别名: 1-lauroyl-2-hydroxy-sn-glycero-3-phosphocholine；1-O-dodecanoyl-sn-glycero-3-phosphocholine；lauroyl L-lysophosphatidylcholine；lauroyl-lysophosphatidylcholine；lysolecithin；LysoFos-12；1-Dodecanoyl-sn-glycero-3-phosphocholine；[(2R)-3-dodecanoyloxy-2-hydroxypropyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 20559-18-6
• 化学式: C₂₀H₄₂NO₇P
• 分子量: 439.53
• InChiKey: BWKILASWCLJPBO-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• WGK Germany：
  3
• 海关编码：
  2923900090
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P501,P270,P202,P201,P264,P280,P308+P313,P301+P310+P330,P405
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H361
• 储存条件：
  -20°C

反应信息

• 作为反应物：
  描述：

  4-联苯乙酸 、 月桂酰溶血磷酰脂 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以60%的产率得到1-dodecanoyl-2-(2-(4-biphenyl)acetyl)-sn-glycero-3-phosphocholine
  参考文献：
  名称：

  具有正磁化率各向异性的磷脂双胞胎

  摘要：

  这篇通讯描述了一种新型的双细胞，它们的主轴与外部磁场平行。磷脂双胞胎是通过混合适当比例的长链磷脂形成的圆盘状双层胶束 1，例如 1,2-ditetradecanoylsn-glycero-3-phosphocholine（DMPC，其中 M 代表肉豆蔻酰基）或 1,2-didodecylsn-甘油-3-磷酸胆碱（DLPC，其中 L 代表月桂酰）与短链磷脂，如 1,2-二己酰基-n-甘油-3-磷酸胆碱 (DHPC)，在水性介质中。正常的双细胞体系在水中含有约 5 -40% w/v 的磷脂酰胆碱，并在环境温度下呈现向列相。当二酰基磷脂中的酯键被醚键取代时，二纤维素对 pH 变化更稳定。2

  DOI：

  10.1021/ja005605+
• 作为产物：
  描述：

  月桂酰氯 、 甘磷酸胆碱 在 二正丁基氧化锡 、 TEA 作用下， 以 异丙醇 为溶剂， 反应 1.58h， 以97%的产率得到月桂酰溶血磷酰脂
  参考文献：
  名称：

  锡介导的溶血磷脂合成。

  摘要：

  从相应的二醇，甘油磷酰基胆碱和3-磷酸甘油中，选择性地且高收率地制备了1-O-酰基-sn-甘油-3-磷酸胆碱和1-O-酰基-sn-甘油-3-磷酸。由二醇开始，在2-丙醇中通过与二烷基氧化锡反应制备活化的锡缩酮。在相同的溶剂中用长链脂肪酸氯化物酰化中间体，从而以高收率和完全的区域选择性得到相应的1-酰基-溶血磷脂。讨论了锡介导的酰化反应的催化性质和溶剂的相关性。

  DOI：

  10.1039/b604636c

文献信息

• Phospholipid Bicelles That Align with Their Normals Parallel to the Magnetic Field
  作者：Chibing Tan、B. M. Fung、Gyoujin Cho

  DOI：10.1021/ja027079n

  日期：2002.10.1

  recently reported phospholipid bicelles (bilayered micelles) that have positive anisotropy of the magnetic susceptibility and align with their normals parallel to an external magnetic field [J. Am. Chem. Soc. 2001, 123, 1537]. Improvements have been made via the synthesis of a new phospholipid, 1-dodecanoyl-2-(4-(4-biphenyl)butanoyl)-sn-glycero-3-phosphocholine (DBBPC). Bicelles can be formed by mixing

  我们最近报道了具有正磁化率各向异性并与平行于外部磁场的法线对齐的磷脂双胞胎（双层胶束）[J. 是。化学 社会。2001, 123, 1537]。通过合成新的磷脂 1-dodecanoyl-2-(4-(4-biphenyl)butanoyl)-sn-glycero-3-phosphocholine (DBBPC) 进行了改进。Bicelles 可以通过在水性介质中以 5.1:1 和 6.5:1 的比例混合 DBBPC 与短链磷脂、1,2-二己酰基-sn-甘油-3-磷酸胆碱 (DHPC) 来形成。(31)P NMR 光谱清楚地表明，这些双胞胎在很宽的温度范围内与平行于磁场的主轴对齐。(31)P 化学位移表明这些双胞胎中极性头基的构象可能与普通双胞胎中的不同。使用 (31) P、(2) H 和 (23) Na NMR 在 10-75 摄氏度的温度范围内研究了 DBBPC/DHPC 混合物与 6:1
• Application of³¹P NMR spectroscopy and chemical derivatization for metabolite profiling of lipophilic compounds in human serum
  作者：M. Aruni DeSilva、Narasimhamurthy Shanaiah、G. A. Nagana Gowda、Kellymar Rosa-Pérez、Bryan A. Hanson、Daniel Raftery

  DOI：10.1002/mrc.2480

  日期：2009.12

  using the derivatizing agent 2‐chloro‐4,4,5,5‐tetramethyldioxaphospholane. Lipids containing hydroxyl, aldehyde and carboxyl groups were selectively tagged with 31P and then detected with good resolution using 31P NMR by exploiting the 100% natural abundance and wide chemical shift range of 31P. After standardizing the reaction conditions using representative compounds, the derivatization approach was

  对于早期疾病检测、人类健康和病理生理学研究以及更好地了解系统生物学，高度寻求获得具有更高分辨率和灵敏度的生物样品代谢指纹的新方法。考虑到生物样品的复杂性，通过使用化学选择性探针来提高分辨率和定量来选择生化类别的兴趣正在增加。考虑到脂质在许多疾病的发病机制中的作用，在本研究中，脂质代谢物的指纹图谱是通过使用衍生剂 2-氯-4,4,5,5-四甲基二氧杂膦的 31P 标记实现的。含羟基的脂质，醛和羧基被 31P 选择性标记，然后利用 31P NMR 利用 31P 的 100% 天然丰度和宽化学位移范围以良好的分辨率进行检测。在使用代表性化合物标准化反应条件后，衍生化方法用于分析人血清中的脂质。结果表明，31P 衍生化方法简单、重现性好且定量性高，有可能对复杂生物样品中的许多重要脂质进行分析。版权所有 © 2009 John Wiley & Sons, Ltd. 并且有可能分析复杂生物样品中的许多重要脂质。版权所有
• Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity
  作者：Daisuke Hishikawa、Hideo Shindou、Saori Kobayashi、Hiroki Nakanishi、Ryo Taguchi、Takao Shimizu

  DOI：10.1073/pnas.0712245105

  日期：2008.2.26

  All organisms consist of cells that are enclosed by a cell membrane containing bipolar lipids and proteins. Glycerophospholipids are important not only as structural and functional components of cellular membrane but also as precursors of various lipid mediators. Polyunsaturated fatty acids comprising arachidonic acid or eicosapentaenoic acid are located at sn -2 position, but not at sn -1 position of glycerophospholipids in an asymmetrical manner. In addition to the asymmetry, the membrane diversity is important for membrane fluidity and curvature. To explain the asymmetrical distribution of fatty acids, the rapid turnover of sn -2 position was proposed in 1958 by Lands [Lands WE (1958) Metabolism of glycerolipides: A comparison of lecithin and triglyceride synthesis. J Biol Chem 231:883–888]. However, the molecular mechanisms and biological significance of the asymmetry remained unknown. Here, we describe a putative enzyme superfamily consisting mainly of three gene families, which catalyzes the transfer of acyl-CoAs to lysophospholipids to produce different classes of phospholipids. Among them, we characterized three important enzymes with different substrate specificities and tissue distributions; one, termed lysophosphatidylcholine acyltransferase-3 (a mammalian homologue of Drosophila nessy critical for embryogenesis), prefers arachidonoyl-CoA, and the other two enzymes incorporate oleoyl-CoAs to lysophosphatidylethanolamine and lysophosphatidylserine. Thus, we propose that the membrane diversity is produced by the concerted and overlapped reactions with multiple enzymes that recognize both the polar head group of glycerophospholipids and various acyl-CoAs. Our findings constitute a critical milestone for our understanding about how membrane diversity and asymmetry are established and their biological significance.

  所有生物体都由细胞组成，这些细胞被包含双极脂质和蛋白质的细胞膜所包围。甘油磷脂不仅作为细胞膜的结构和功能组成部分，还是各种脂质介质的前体。由花生四烯酸或二十碳五烯酸组成的多不饱和脂肪酸位于甘油磷脂的不对称的sn-2位置，而不是sn-1位置。除了不对称性外，膜的多样性对于膜的流动性和曲率也很重要。为了解释脂肪酸的不对称分布，1958年Lands提出了sn-2位置的快速周转。然而，不对称性的分子机制和生物学意义仍然未知。在这里，我们描述了一个潜在的酶超家族，主要由三个基因家族组成，它们催化酰基辅酶A转移至溶血磷脂，以产生不同类别的磷脂。其中，我们表征了三种具有不同底物特异性和组织分布的重要酶；一种被称为溶血磷脂酰转移酶-3（果蝇nessy的哺乳动物同源物，对胚胎发育至关重要），更喜欢花生四烯酰辅酶A，而另外两种酶则将油酰辅酶A并入到溶血磷脂酰乙醇胺和溶血磷脂酰丝氨酸中。因此，我们提出，膜的多样性是由多个酶的协同和重叠反应产生的，这些酶识别甘油磷脂的极性头基和各种酰基辅酶A。我们的发现对于我们理解膜的多样性和不对称性的建立及其生物学意义构成了一个关键的里程碑。
• Structural basis of substrate discrimination and integrin binding by autotaxin
  作者：Jens Hausmann、Satwik Kamtekar、Evangelos Christodoulou、Jacqueline E Day、Tao Wu、Zachary Fulkerson、Harald M H G Albers、Laurens A van Meeteren、Anna J S Houben、Leonie van Zeijl、Silvia Jansen、Maria Andries、Troii Hall、Lyle E Pegg、Timothy E Benson、Mobien Kasiem、Karl Harlos、Craig W Vander Kooi、Susan S Smyth、Huib Ovaa、Mathieu Bollen、Andrew J Morris、Wouter H Moolenaar、Anastassis Perrakis

  DOI：10.1038/nsmb.1980

  日期：2011.2

  The enzyme autotaxin (ATX) produces the lipid mediator LPA to stimulate cell migration and proliferation. The crystal structures of rat ATX, in its apo and inhibitor-bound forms, along with functional work, offer insight into substrate specificity and show that ATX interacts with integrins through one of its SMB domains. Autotaxin (ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase-2, ENPP2) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX-LPA signaling is involved in various pathologies including tumor progression and inflammation. However, the molecular basis of substrate recognition and catalysis by ATX and the mechanism by which it interacts with target cells are unclear. Here, we present the crystal structure of ATX, alone and in complex with a small-molecule inhibitor. We have identified a hydrophobic lipid-binding pocket and mapped key residues for catalysis and selection between nucleotide and phospholipid substrates. We have shown that ATX interacts with cell-surface integrins through its N-terminal somatomedin B–like domains, using an atypical mechanism. Our results define determinants of substrate discrimination by the ENPP family, suggest how ATX promotes localized LPA signaling and suggest new approaches for targeting ATX with small-molecule therapeutic agents.

  酶autotaxin（ATX）产生脂质介质LPA，以刺激细胞迁移和增殖。大鼠ATX的晶体结构（包括无配体和与抑制剂结合的形式）以及功能研究，有助于深入了解底物特异性，并表明ATX通过其SMB结构域之一与整合素相互作用。Autotaxin（ATX，也称为外核苷酸焦磷酸酶/磷酸二酯酶-2，ENPP2）是一种分泌的溶血磷脂酶D，可产生脂质介质溶血磷脂酸（LPA），后者是多种细胞的促分裂素和趋化因子。ATX-LPA信号传导与多种病理有关，包括肿瘤进展和炎症。然而，ATX识别底物和催化的分子基础以及其与靶细胞相互作用的机制尚不清楚。在此，我们展示了ATX的晶体结构，包括单独的以及与小分子抑制剂结合的晶体结构。我们鉴定了一个疏水性脂质结合口袋，并绘制了催化以及核苷酸和磷脂底物之间选择的关键残基。我们表明，ATX通过其N端类似生长抑素B的结构域与细胞表面整合素相互作用，采用了一种非典型的机制。我们的研究结果确定了ENPP家族底物识别的决定因素，揭示了ATX如何促进局部LPA信号传导，并提出了用小分子治疗剂靶向ATX的新方法
• 2-(Tributylstannyl)-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl Alcohol: A Building Block for Photolabeling and Crosslinking Reagents of Very High Specific Radioactivity
  作者：Thomas Weber、Josef Brunner

  DOI：10.1021/ja00116a013

  日期：1995.3

  A general approach for the synthesis of novel, radioiodinated photolabeling and cross-linking reagents at no-carrier-added (nea) specific radioactivity (> 2000 Ci/mmol) is described. In this approach, 2-(tributylstannyl)-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl alcohol 12 serves as a module which, through acylation of its alcohol function, is connected to other structural/functional elements to make the tin-containing precursor forms of the reagents. The final, radioactive compounds are then conveniently prepared in yields varying from 15-50% by electrophilic aromatic substitution of the tributylstannyl group by I-125(+) generated in situ from I-125(-) by peracetic acid. Using this approach, we have synthesized two analogues of phosphatidylcholine (PC) (20 and 21), an analogue of ceramide (36), as well as two heterobifunctional label-transfer cross-linkers (29 and 33). PC 21, examined more closely, is a substrate of the PC-specific phospholipid exchange protein from beef liver and of phospholipase D from cabbage. The latter was utilized to enzymatically convert PC 21 into two additional phospholipids, phosphatidylserine (PS) 25 and phosphatidic acid (PA) 26. Reagents that contain this iodinated photophor also combine desirable photochemical properties. Thus, evidence is presented that they undergo efficient photolysis to generate a (singlet) carbene intermediate which inserts efficiently into hydrocarbon CH bonds. In addition, we demonstrate that the diazirine can be photolyzed in a selective manner, that is, without photodeiodination to occur to a significant extent.