2-Amino-3-hydroxyoctadec-4-en-1-yl 2-(trimethylazaniumyl)ethyl phosphate | 1670-26-4

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: 2-Amino-3-hydroxyoctadec-4-en-1-yl 2-(trimethylazaniumyl)ethyl phosphate
• 英文别名: [(E,2S,3R)-2-azaniumyl-3-hydroxyoctadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 1670-26-4
• 化学式: C23H50N2O5P+
• 分子量: 465.6
• InChiKey: JLVSPVFPBBFMBE-HXSWCURESA-O

物化性质

• 熔点：
  90-102°C
• 溶解度：
  在氯仿/甲醇(2:1)中的溶解度:10mg/ml,无色至淡黄色
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  水 、 2-Amino-3-hydroxyoctadec-4-en-1-yl 2-(trimethylazaniumyl)ethyl phosphate 生成 氢(+1)阳离子 、 phosphocholine 、 Sphingosine(1+)
  参考文献：
  名称：

  Biochemical and Molecular Characterization of a Novel Choline-specific Glycerophosphodiester Phosphodiesterase Belonging to the Nucleotide Pyrophosphatase/Phosphodiesterase Family

  摘要：

  Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that release nucleoside 5'-monophosphate from a variety of nucleotides and nucleotide derivatives. The mammalian NPP family comprises seven members, but only three of these (NPP1-3) have been studied in some detail. Previously we showed that lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid, is identical to NPP2. More recently an uncharacterized novel NPP member (NPP7) was shown to have alkaline sphingomyelinase activity. These findings raised the possibility that other members of the NPP family act on phospholipids. Here we show that the sixth member of the NPP family, NPP6, is a choline-specific glycerophosphodiester phosphodiesterase. The sequence of NPP6 encodes a transmembrane protein containing an NPP domain with significant homology to NPP4, NPP5, and NPP7/alkaline sphingomyelinase. When expressed in HeLa cells, NPP6 was detected in both the cells and the cell culture medium as judged by Western blotting and by enzymatic activity. Recombinant NPP6 efficiently hydrolyzed the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine, but not the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. In addition, NPP6 hydrolyzed LPC to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. NPP6 showed a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. It also hydrolyzed glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. In mice, NPP6 mRNA was predominantly detected in kidney with a lesser expression in brain and heart, and in human it was detected in kidney and brain. The present results suggest that NPP6 has a specific role through the hydrolysis of polyunsaturated LPC, glycerophosphorylcholine, or sphingosylphosphorylcholine in these organs.

  DOI：

  10.1074/jbc.m413438200
• 作为产物：
  描述：

  a sphingomyelin 、 水 生成 a carboxylate 、 2-Amino-3-hydroxyoctadec-4-en-1-yl 2-(trimethylazaniumyl)ethyl phosphate
  参考文献：
  名称：

  High-Expression of Sphingomyelin Deacylase is an Important Determinant of Ceramide Deficiency Leading to Barrier Disruption in Atopic Dermatitis1

  摘要：

  We have previously demonstrated that there is abnormal expression of sphingomyelin (SM) deacylase-like enzyme in the epidermis of patients with atopic dermatitis (AD), which results in decreased levels of ceramides in their involved and uninvolved stratum corneum, For quantitation of the expression of SM deacylase in AD, we synthesized 16-(9-anthroyloxy) hexadecanoylsphingosylphosphorylcholine or [palmitic acid-C-14] SM and used them as substrates to directly measure the activity of SM deacylase by detecting the release of labeled free fatty acid. Direct enzymatic measurements demonstrated that stratum corneum from lesional forearm skin (volar side) of AD patients has an extremely high SM deacylase activity that is at least five times higher than in the stratum corneum from healthy controls. In stratum corneum from nonlesional skin of AD patients, SM deacylase activity is still at least three times higher than in healthy controls. In contrast, stratum corneum from contact dermatitis patients shows levels of SM deacylase similar to healthy controls. In extracts of whole epidermis biopsies from AD patients, SM deacylase activities are significantly (3-fold) increased over healthy controls in the particulate fraction, whereas there is no significant difference in the activity of sphingomyelinase between AD and healthy control. In peripheral blood lymphocytes of AD patients, there is no increase in activity compared with healthy controls, indicating a possibility that the high expression of SM deacylase is highly associated with the skin of AD patients. These findings suggest that, in contrast to changes in sphingolipid metabolism due to aging, the hitherto undiscovered enzyme SM deacylase, is highly expressed in the epidermis of AD patients, and competes with sphingomyelinase or beta-glucocerebrosidase for the common substrate SM or glucosylceramide, which leads to the ceramide deficiency of the stratum corneum in AD.

  DOI：

  10.1046/j.1523-1747.2000.00072.x

文献信息

• Compounds and methods of use thereof for assaying lysophospholipase D activity
  申请人：Echelon Biosciences Incorporated

  公开号：US20040171096A1

  公开（公告）日：2004-09-02

  Fluorogenic lysophosphatidic acid derivatives which can be used as substrates in a continuous, fluorogenic assay that can be performed in microtiter plates. The assays permit measuring LysoPLD activity levels in normal events such as pregnancy or disease states such as cancer. In addition, the present invention can be adopted to high throughout screening(HTS) for identification of potential inhibitors of lysoPLD activity.

  可以用作底物的荧光型溶血磷脂酸衍生物，可在微孔板中进行连续的荧光测定。该测定可用于测量正常事件（如妊娠）或疾病状态（如癌症）中的溶血磷脂酸酯酶（LysoPLD）活性水平。此外，本发明可用于高通量筛选（HTS），以鉴定潜在的溶血磷脂酸酯酶抑制剂。
• Compositions for the treatment of diseases associated with elevated sphingolipid concentrations
  申请人：Medlyte, Inc.

  公开号：EP1731161A1

  公开（公告）日：2006-12-13

  Methods and compositions are disclosed that are useful for the prevention and/or treatment of cardiovascular and cardiac diseases and disorders, or damage resulting from surgical or medical procedures that may cuase ischemic or ischemic/reperfusion damage in humans; and cardiovascular trauma. The beneficial effects of the compositions and methods are achieved through the use of pharmaceutical compositions that include agents that interfere with the production and/or biological activities of sphingolipids and their metabolites, particularly sphingosine (SPH) and sphingosine-1-phosphate (S-1-P). Also disclosed are methods for identifying and isolating therapeutic agents.

  本发明公开了一些方法和组合物，可用于预防和/或治疗心血管和心脏疾病和失调，或可能导致人体缺血或缺血/再灌注损伤的手术或医疗程序造成的损伤，以及心血管创伤。本发明组合物和方法的有益效果是通过使用药物组合物实现的，药物组合物包括干扰鞘磷脂及其代谢物，特别是鞘磷脂（SPH）和鞘磷脂-1-磷酸（S-1-P）的产生和/或生物活性的制剂。还公开了用于鉴定和分离治疗剂的方法。
• Methods for distributing high levels of therapeutic agent throughout the cortex to treat neurological disorders
  申请人：Bankiewicz Krystof

  公开号：US11305022B2

  公开（公告）日：2022-04-19

  The invention provides methods for treating neurological disorders, which involve administering therapeutic agents to the thalamus by convection enhanced delivery.

  本发明提供了治疗神经系统疾病的方法，其中包括通过对流增强输送将治疗剂输送到丘脑。
• Compositions and methods for the treatment and prevention of cardiovascular diseases and disorders, and for identifying agents therapeutic therefor
  申请人：Medlyte, Inc.

  公开号：US20030026799A1

  公开（公告）日：2003-02-06

  Methods and compositions are disclosed that are useful for the prevention and/or treatment of cardiovascular and cardiac diseases and disorders, or damage resulting from surgical or medical procedures that may cause ischemic or ischemic/reperfusion damage in humans; and cardiovascular trauma. The beneficial effects of the compositions and methods are achieved through the use of pharmaceutical compositions that include agents that interfere with the production and/or biological activities of sphingolipids and their metabolites, particularly sphingosine (SPH) and sphingosine-1-phosphate (S-1-P). Also disclosed are methods for identifying and isolating therapeutic agents.

  所公开的方法和组合物有助于预防和/或治疗心血管和心脏疾病和失调，或可能导致人体缺血或缺血/再灌注损伤的手术或医疗程序造成的损伤；以及心血管创伤。这些组合物和方法的有益效果是通过使用药物组合物实现的，这些组合物包括干扰鞘磷脂及其代谢物，特别是鞘磷脂（SPH）和鞘磷脂-1-磷酸（S-1-P）的产生和/或生物活性的制剂。还公开了用于鉴定和分离治疗剂的方法。
• Universal readout for target identification using biological microarrays
  申请人：——

  公开号：US20040185445A1

  公开（公告）日：2004-09-23

  A method and apparatus for implementing the method is provided. The method involves performing an indirect competitive binding assay on a microarray to identify biological or chemical targets and screen for compounds of interest. The microarray comprises a common ligand located among membrane-, lipid- or protein-associated active binding sites. The method takes advantage of known or well-characterized binding kinetics, and steric interference between biological or chemicals targets of interest and universal readout units for different binding sites within the limited confines of a microspot. The biological targets, chemicals or organisms can specifically bind to target-binding sites, while the universal readout unit binds to the ligands in the microspot.

  本文提供了一种方法和用于实施该方法的装置。该方法包括在微阵列上进行间接竞争性结合测定，以确定生物或化学靶标并筛选感兴趣的化合物。微阵列包括位于膜、脂质或蛋白质相关活性结合位点的共同配体。该方法利用了已知或表征良好的结合动力学，以及感兴趣的生物或化学靶标与微点有限范围内不同结合位点的通用读出单元之间的立体干扰。生物靶标、化学物质或生物体可特异性地与靶标结合位点结合，而通用读出单元则与微点中的配体结合。