N-木香油基-D-赤型-鞘氨醇 | 6063-36-1

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 中文名称: N-木香油基-D-赤型-鞘氨醇
• 英文名称: Cer (d18:0/24:0)
• 英文别名: N-[(2S,3R)-1,3-dihydroxyoctadecan-2-yl]tetracosanamide
• CAS: 6063-36-1
• 化学式: C₄₂H₈₅NO₃
• 分子量: 652.142
• InChiKey: BPLYVSYSBPLDOA-WVILEFPPSA-N

物化性质

• 溶解度：
  二甲基甲酰胺：0.15mg/mL
• 物理描述：
  Solid
• 碰撞截面：
  279.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with phosphatidylcholines (ESI+) and phosphatidylethanolamines (ESI-)]

计算性质

• 辛醇/水分配系数(LogP)：
  17.7
• 重原子数：
  46
• 可旋转键数：
  39
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.98
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-木香油基-D-赤型-鞘氨醇 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 偶氮二甲酸二异丙酯 、 双氧水 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 23.0h， 生成 (2R,3R) 3-hydroxy-2-stearamidooctadecane-1-sulfonic acid
  参考文献：
  名称：

  Synthesis of the Rosette-Inducing Factor RIF-1 and Analogs

  摘要：

  Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development.

  DOI：

  10.1021/ja5046692
• 作为产物：
  描述：

  十四酰鞘氨醇 在 甲醇 、 铂 作用下， 60.0 ℃ 、392.24 kPa 条件下， 生成 N-木香油基-D-赤型-鞘氨醇
  参考文献：
  名称：

  Studies on the Structure of Sphingomyelin. IV. Configuration of the Double Bond in Sphingomyelin and Related Lipids and a Study of their Infrared Spectra

  摘要：

  DOI：

  10.1021/ja01634a047

文献信息

• Lipidomic Biomarkers for Identification of High-Risk Coronary Artery Disease Patients
  申请人：ZORA BIOSCIENCES OY

  公开号：US20160025751A1

  公开（公告）日：2016-01-28

  The present invention inter alia provides a method, and use thereof, of predicting severe CVD complications such as AMI or CVD death by detecting the lipid concentrations or lipid ratios of a biological sample and comparing it to a control and has identified specific lipid markers that are more specific and sensitive in predicting these CVD complications than currently utilized clinical markers. Also provided is an antibodies towards said lipids, and the use thereof for predicting, diagnosing, preventing and/or treating CVD complications. The invention additionally relates to kits comprising lipids and/or an antibody thereto, for use in the prediction and/or diagnosis of CVD complications.

  本发明提供了一种方法及其使用，通过检测生物样品的脂质浓度或脂质比值并将其与对照组进行比较，预测严重的心血管疾病并发症，如心肌梗死或心血管死亡，并确定了比目前使用的临床标志更具特异性和敏感性的特定脂质标记。同时，还提供了针对上述脂质的抗体及其使用，用于预测、诊断、预防和/或治疗心血管疾病并发症。本发明还涉及包含脂质和/或其抗体的试剂盒，用于预测和/或诊断心血管疾病并发症。
• LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity
  作者：Yukiko Mizutani、Akio Kihara、Yasuyuki Igarashi

  DOI：10.1042/bj20060379

  日期：2006.9.15

  The LASS (longevity assurance homologue) family members are highly conserved from yeasts to mammals. Five mouse and human LASS family members, namely LASS1, LASS2, LASS4, LASS5 and LASS6, have been identified and characterized. In the present study we cloned two transcriptional variants of hitherto-uncharacterized mouse LASS3 cDNA, which encode a 384-amino-acid protein (LASS3) and a 419-amino-acid

  LASS（长寿保证同源物）家族成员从酵母到哺乳动物都是高度保守的。已鉴定并鉴定了五个小鼠和人类LASS家族成员，即LASS1，LASS2，LASS4，LASS5和LASS6。在本研究中，我们克隆了迄今未表征的小鼠LASS3 cDNA的两个转录变异体，它们编码384个氨基酸的蛋白质（LASS3）和419个氨基酸的蛋白质（LASS3长）。在体内，[3H]二氢鞘氨醇标记和电喷雾电离质谱显示，任何一种LASS3同工型的过量生产都会导致几种神经酰胺的增加，其中有些偏向于具有中链至长链脂肪酰基-CoA的那些。在体外（二氢）神经酰胺合酶测定中观察到相似的底物偏好。这些结果表明LASS3具有（二氢）神经酰胺合成活性，具有相对宽的底物特异性。我们还发现，除了在皮肤中的弱展示外，LASS3 mRNA的表达几乎仅限于睾丸，这表明LASS3在该腺体中起着重要的作用。
• Loss of ceramide synthase 3 causes lethal skin barrier disruption
  作者：Richard Jennemann、Mariona Rabionet、Karin Gorgas、Sharon Epstein、Alexander Dalpke、Ulrike Rothermel、Aline Bayerle、Franciscus van der Hoeven、Silke Imgrund、Joachim Kirsch、Walter Nickel、Klaus Willecke、Howard Riezman、Hermann-Josef Gröne、Roger Sandhoff

  DOI：10.1093/hmg/ddr494

  日期：2012.2.1

  The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1–6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

  作为最外层表皮层的角质层可防止干燥和感染。 角质层下角质包膜（CE）和细胞间脂质基质是这两层主要保护屏障的主要组成部分。 表皮特有的具有超长链酰基（ULC-Cer）的神经酰胺是细胞外脂质层（ELL）的关键组成部分，并与CE蛋白结合，从而形成角质脂质包膜（CLE）。 在这里，我们确定了人类和鼠神经酰胺合成酶3（CerS3），在CerS1-6中，CerS3是体外ULC-Cer合成和体内小鼠CerS3合成的唯一必需成分。 小鼠CerS3的缺乏会导致ULC-Cer（≥C26）的完全丧失，缺乏连续的ELL和无法发挥功能的CLE。 因此，新生突变小鼠在出生后不久就会因表皮水分流失而死亡。 突变皮肤容易感染白色念珠菌，这表明ULC-Cer对于这两种屏障功能至关重要。 持续性外皮、角化过度和角质化不足是突变皮肤的特征，表明神经酰胺的丧失会导致角质形成细胞在胚胎屏障前阶段成熟停滞。
• Mammalian Lass6 and its related family members regulate synthesis of specific ceramides
  作者：Yukiko Mizutani、Akio Kihara、Yasuyuki Igarashi

  DOI：10.1042/bj20050291

  日期：2005.8.15

  The Lass (longevity-assurance homologue) family members, which are highly conserved among eukaryotes, function in ceramide synthesis. In the mouse, there are at least five Lass family members, Lass1, Lass2, Lass4, Lass5 and the hitherto uncharacterized Lass6. To investigate specific roles for each Lass member in ceramide synthesis, we cloned these five mouse proteins. Overproduction of any Lass protein in cultured cells resulted in an increase in cellular ceramide, but the ceramide species produced varied. Overproduction of Lass1 increased C18:0-ceramide levels preferentially, and overproduction of Lass2 and Lass4 increased levels of longer ceramides such as C22:0- and C24:0-ceramides. Lass5 and Lass6 produced shorter ceramide species (C14:0- and C16:0-ceramides); however, their substrate preferences towards saturated/unsaturated fatty acyl-CoA differed. In addition to differences in substrate preferences, we also demonstrated by Northern blotting that Lass family members are differentially expressed among tissues. Additionally, we found that Lass proteins differ with regard to glycosylation. Of the five members, only Lass2, Lass5 and Lass6 were N-glycosylated, each at their N-terminal Asn residue. The occurrence of N-glycosylation of some Lass proteins provides topological insight, indicating that the N-termini of Lass family members probably face the luminal side of the endoplasmic reticulum membrane. Furthermore, based on a proteinase K digestion assay, we demonstrated that the C-terminus of Lass6 faces the cytosolic side of the membrane. From these data we propose topology for the conserved Lag1 motif in Lass family members, namely that the N-terminal region faces the luminal side and the C-terminal region the cytosolic side of the endoplasmic reticulum membrane.

  Lass（长寿保证同源物）家族成员在真核生物中高度保守，在神经酰胺合成中发挥作用。在小鼠体内，至少有五个 Lass 家族成员，即 Lass1、Lass2、Lass4、Lass5 和迄今尚未定性的 Lass6。为了研究每个 Lass 成员在神经酰胺合成中的特定作用，我们克隆了这五种小鼠蛋白。在培养细胞中过度生产任何一种 Lass 蛋白都会导致细胞神经酰胺的增加，但产生的神经酰胺种类各不相同。过量生产 Lass1 会优先增加 C18:0 神经酰胺的含量，而过量生产 Lass2 和 Lass4 则会增加较长神经酰胺的含量，如 C22:0 和 C24:0 神经酰胺。Lass5 和 Lass6 产生较短的神经酰胺种类（C14:0- 和 C16:0-神经酰胺）；但是，它们对饱和/不饱和脂肪酰基-CoA 的底物偏好不同。除了底物偏好的差异，我们还通过 Northern 印迹技术证明了 Lass 家族成员在不同组织中的表达差异。此外，我们还发现 Lass 蛋白在糖基化方面存在差异。在五个成员中，只有 Lass2、Lass5 和 Lass6 在其 N 端 Asn 残基上进行了 N-糖基化。一些 Lass 蛋白发生 N-糖基化提供了拓扑学上的启示，表明 Lass 家族成员的 N 端可能面向内质网膜的腔侧。此外，基于蛋白酶 K 消化试验，我们证明 Lass6 的 C 端面向膜的细胞质一侧。根据这些数据，我们提出了 Lass 家族成员中保守的 Lag1 基序的拓扑结构，即 N 端区域面向内质网膜的腔侧，C 端区域面向内质网膜的细胞质侧。
• Characterization of Ceramide Synthase 2
  作者：Elad L. Laviad、Lee Albee、Irene Pankova-Kholmyansky、Sharon Epstein、Hyejung Park、Alfred H. Merrill、Anthony H. Futerman

  DOI：10.1074/jbc.m707386200

  日期：2008.2

  CoAs (C20-C26) for ceramide synthesis. There is a good correlation between CerS2 mRNA levels and levels of ceramide and sphingomyelin containing long acyl chains, at least in tissues where CerS2 mRNA is expressed at high levels. Interestingly, the activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part

  神经酰胺是重要的脂质信号分子，是鞘脂生物合成中的关键中间体。最近的研究暗示了神经酰胺N-酰基链长的作用是前所未有的，因为含有特定脂肪酸的神经酰胺似乎在细胞生理学中起着确定的作用。哺乳动物神经酰胺合酶（CerS）家族的发现加强了这一观念，每个家族都利用酰基辅酶A的一个有限子集进行神经酰胺合成。现在，我们报告哺乳动物CerS2的表征。qPCR分析表明，在所有CerS中，CerS2 mRNA的含量最高，并且组织分布最广。CerS2具有出色的酰基CoA特异性，使用C16：0-CoA时无活性，而使用C18：0则显示低活性，而是利用更长的酰基链CoA（C20-C26）进行神经酰胺合成。至少在高水平表达CerS2 mRNA的组织中，CerS2 mRNA水平与含有长酰基链的神经酰胺和鞘磷脂水平之间存在良好的相关性。有趣的是，CerS2的活性可以通过另一种生物活性鞘脂，1-磷酸鞘氨醇（S1P）来调节，这是通