trans-4,cis-8-sphingadienine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-4,cis-8-sphingadienine
• 英文别名: sphinga-4E,8Z-dienine；(2S,3R,4E,8Z)-2-aminooctadeca-4,8-diene-1,3-diol
• 化学式: C₁₈H₃₅NO₂
• 分子量: 297.481
• InChiKey: RTQVJTLVVBJRJG-NZDSQIAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  棕榈酸酐 、 trans-4,cis-8-sphingadienine 以 甲醇 为溶剂， 反应 22.0h， 以2 mg的产率得到N-hexadecanoylsphinga-(4E,8Z)-dienine
  参考文献：
  名称：

  Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species

  摘要：

  魔芋酸二酰胺（kCer）由具有特征性shingoid碱基和脂肪酸的植物型分子种类组成，通过化酶去葡萄糖化从魔芋葡糖鞘氨醇GlcCer制备而成。kCer激活semaforin 3A（Sema3A）信号通路，诱导崩塌反应介导蛋白2（CRMP2）的磷酸化。这导致PC12细胞中神经突起生长受抑制，剩余长神经突起形态发生变化。特定的kCer分子种类是否能与Sema3A受体（神经丝蛋白1，Nrp1）结合并激活Sema3A信号通路目前尚不清楚。在这里，我们使用内葡糖鞘氨醇酶I介导的去葡萄糖化制备了kCer分子种类，并检查了在神经生长因子（NGF）预处理的细胞中神经突起生长和崩塌反应介导蛋白2的磷酸化。kCer的鞘二烯醇8-反式不饱和对于Sema3A类似信号通路的激活至关重要。相反，kCer分子种类的鞘二烯醇8-顺式不饱和对Sema3A类似激活没有影响，并导致剩余短神经突起的神经突起抑制。此外，脂肪酸的α-羟基化与kCer分子种类的Sema3A类似活性无关。这些结果表明，鞘二烯醇8-反式或8-顺式异构化决定了Nrp1配体结合位点的特定相互作用。

  DOI：

  10.3390/ijms20092116
• 作为产物：
  描述：

  在 盐酸 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 trans-4,cis-8-sphingadienine 、 trans-4,trans-8-sphingadienine
  参考文献：
  名称：

  Characterization of Glucocerebrosides and the Active Metabolite 4,8-Sphingadienine from Arisaema amurense and Pinellia ternata by NMR and CD Spectroscopy and ESI-MS/CID-MS

  摘要：

  Sphingolipid metabolites regulate cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, glucocerebrosides (GluCer) from rhizomes of Arisaema amurense and Pinellia ternata were fully characterized using 1- and 2-dimensional nuclear magnetic spin resonance (NMR) and circular dichroism (CD) spectroscopy and tandem collision induced dissociation mass spectrometry (ESI-MS/CID-MS). Three new acylated and seven known GluCer were elucidated with 4,8-sphingadienine (4,8-SD, d18:2) as backbone. 4,8-SD is a metabolite after enzymatical hydrolysis of GluCer in the gut lumen. In this study, 4,8-SD was hydrolyzed from GluCer and chromatographically purified on silica gel. In contrast to the GluCer, 4,8-SD showed cytotoxic effects in the WST-1 assay. GluCer with 4,8-SD as sphingoid backbone are present in plants consumed as food, such as spinach, soy, and eggplant.

  DOI：

  10.1021/jf302085u

文献信息

• Development of an LC–MS/MS Method for the Analysis of Free Sphingoid Bases Using 4-Fluoro-7-nitrobenzofurazan (NBD-F)
  作者：Toshiki Ishikawa、Hiroyuki Imai、Kawai-Yamada Maki

  DOI：10.1007/s11745-013-3871-6

  日期：2014.3

  species of free sphingoid bases present in plant sphingolipids were separated and quantified for the first time; a complete baseline resolution was achieved for cis‐8 and trans‐8 isomers of sphingoid bases by reversed phase HPLC on a C18 column. The extraction and derivatization procedures and LC–MS/MS method can facilitate the progress of the studies for seeking the active components of sphingoid bases

  鞘氨醇碱基的分子种类用荧光氨基试剂4-氟-7-硝基苯并呋喃（NBD-F）标记。通过高度选择性和灵敏的液相色谱-电喷雾电离串联质谱（LC-ESI-MS / MS）技术对NBD鞘氨醇碱基进行了分析，该技术能够可靠地检测几种fmol的衍生物。用NBD-F衍生化了植物样品中的脂质提取物，首次分离并定量了植物鞘脂中存在的所有9种游离鞘氨醇碱基；通过在C 18上进行反相HPLC可以实现鞘氨醇碱基的顺式8和反式8异构体的完整基线分离柱。提取和衍生化步骤以及LC-MS / MS方法可以促进研究寻找鞘氨醇碱类物种的活性成分以应对生物学挑战的研究进展。
• MICROFLUIDIC PRODUCTION OF BIOFUNCTIONALIZED GIANT UNILAMELLAR VESICLES FOR TARGETED INTRACELLULAR CARGO DELIVERY
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP3838266A1

  公开（公告）日：2021-06-23

  The present invention relates to a method for preparation of monodisperse cell-targeting giant unilamellar vesicles based on symmetrically division of a parent polymer shell-stabilized giant unilamellar vesicle into smaller polymer shell-stabilized giant unilamellar vesicles with a diameter smaller than 10 µm using a microfluidic splitting device. The inventive method allows preparation of differently charged giant unilamellar vesicles as well as bioligand- and PEG-conjugated giant unilamellar vesicles, which are useful for targeted cellular delivery at high efficiency and specificity. A further advantage of the present invention is that the giant unilamellar vesicles can deliver huge cargos such as drug releasing porous microparticles, high amounts of in vivo imaging probes, viruses, or up-and-coming DNA origami robots.

  本发明涉及一种制备单分散细胞靶向巨型单拉美米尔囊泡的方法，其基础是利用微流体分割装置将母体聚合物壳稳定巨型单拉美米尔囊泡对称分割成直径小于10微米的较小聚合物壳稳定巨型单拉美米尔囊泡。 本发明的方法可制备不同电荷的巨型单拉米分子囊泡以及生物配体和 PEG 共轭巨型单拉米分子囊泡，这些囊泡可用于高效、特异性的细胞靶向递送。本发明的另一个优点是，巨型单拉美拉尔囊泡可以输送巨大的载体，如释放药物的多孔微颗粒、大量的体内成像探针、病毒或新兴的 DNA 折纸机器人。
• BOTTOM-UP ASSEMBLY OF SYNTHETIC EXTRACELLULAR VESICLES
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP3858332A1

  公开（公告）日：2021-08-04

  The present invention relates to a method for producing synthetic extracellular vesicles comprising a lipid bilayer including at least two lipids, optionally one or more extracellular vesicle associated proteins, and optionally one or more nucleic acid molecules. The inventive synthetic extracellular vesicles are formed by emulsification using a mechanic emulsifier in the form of polymer shell stabilized synthetic extracellular vesicles. The inventive method allows producing synthetic extracellular vesicles miming the composition and function of natural extracellular vesicles. Therefore, synthetic extracellular vesicles with specific protein and nucleic acids compositions are also disclosed herein, as well as their therapeutic uses.

  本发明涉及一种生产合成细胞外囊泡的方法，该囊泡包括一个脂质双分子层，其中至少包括两种脂质、一种或多种细胞外囊泡相关蛋白，以及一种或多种核酸分子。本发明的合成细胞外囊泡是通过使用机械乳化剂乳化形成的聚合物壳稳定合成细胞外囊泡。本发明的方法可以生产出模拟天然细胞外囊泡成分和功能的合成细胞外囊泡。因此，本文还公开了具有特定蛋白质和核酸成分的合成细胞外囊泡及其治疗用途。
• Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species
  作者：Seigo Usuki、Noriko Tamura、Tomohiro Tamura、Kunikazu Tanji、Daisuke Mikami、Katsuyuki Mukai、Yasuyuki Igarashi

  DOI：10.3390/ijms20092116

  日期：——

  Konjac ceramide (kCer), which consists of plant-type molecular species of characteristic shingoid bases and fatty acids, is prepared from konjac glucosylceramide GlcCer by chemoenzymatical deglucosylation. kCer activates the semaphorin 3A (Sema3A) signaling pathway, inducing collapsin response mediator protein 2 (CRMP2) phosphorylation. This results in neurite outgrowth inhibition and morphological changes in remaining long neurites in PC12 cells. Whether a specific molecular species of kCer can bind to the Sema3A receptor (Neuropilin1, Nrp1) and activate the Sema3A signaling pathway remains unknown. Here, we prepared kCer molecular species using endoglycoceramidase I-mediated deglucosylation and examined neurite outgrowth and phosphorylation of collapsin response mediator protein 2 in nerve growth factor (NGF)-primed cells. The 8-trans unsaturation of sphingadienine of kCer was essential for Sema3A-like signaling pathway activation. Conversely, 8-cis unsaturation of kCer molecular species had no effect on Sema3A-like activation, and neurite outgrowth inhibition resulted in remaining short neurites. In addition, α-hydroxylation of fatty acids was not associated with the Sema3A-like activity of the kCer molecular species. These results suggest that 8-trans or 8-cis isomerization of sphingadienine determines the specific interactions at the ligand-binding site of Nrp1.

  魔芋酸二酰胺（kCer）由具有特征性shingoid碱基和脂肪酸的植物型分子种类组成，通过化酶去葡萄糖化从魔芋葡糖鞘氨醇GlcCer制备而成。kCer激活semaforin 3A（Sema3A）信号通路，诱导崩塌反应介导蛋白2（CRMP2）的磷酸化。这导致PC12细胞中神经突起生长受抑制，剩余长神经突起形态发生变化。特定的kCer分子种类是否能与Sema3A受体（神经丝蛋白1，Nrp1）结合并激活Sema3A信号通路目前尚不清楚。在这里，我们使用内葡糖鞘氨醇酶I介导的去葡萄糖化制备了kCer分子种类，并检查了在神经生长因子（NGF）预处理的细胞中神经突起生长和崩塌反应介导蛋白2的磷酸化。kCer的鞘二烯醇8-反式不饱和对于Sema3A类似信号通路的激活至关重要。相反，kCer分子种类的鞘二烯醇8-顺式不饱和对Sema3A类似激活没有影响，并导致剩余短神经突起的神经突起抑制。此外，脂肪酸的α-羟基化与kCer分子种类的Sema3A类似活性无关。这些结果表明，鞘二烯醇8-反式或8-顺式异构化决定了Nrp1配体结合位点的特定相互作用。
• Characterization of Glucocerebrosides and the Active Metabolite 4,8-Sphingadienine from <i>Arisaema amurense</i> and <i>Pinellia ternata</i> by NMR and CD Spectroscopy and ESI-MS/CID-MS
  作者：Evelien Rozema、Ruxandra Popescu、Harald Sonderegger、Christian W. Huck、Johannes Winkler、Georg Krupitza、Ernst Urban、Brigitte Kopp

  DOI：10.1021/jf302085u

  日期：2012.7.25

  Sphingolipid metabolites regulate cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, glucocerebrosides (GluCer) from rhizomes of Arisaema amurense and Pinellia ternata were fully characterized using 1- and 2-dimensional nuclear magnetic spin resonance (NMR) and circular dichroism (CD) spectroscopy and tandem collision induced dissociation mass spectrometry (ESI-MS/CID-MS). Three new acylated and seven known GluCer were elucidated with 4,8-sphingadienine (4,8-SD, d18:2) as backbone. 4,8-SD is a metabolite after enzymatical hydrolysis of GluCer in the gut lumen. In this study, 4,8-SD was hydrolyzed from GluCer and chromatographically purified on silica gel. In contrast to the GluCer, 4,8-SD showed cytotoxic effects in the WST-1 assay. GluCer with 4,8-SD as sphingoid backbone are present in plants consumed as food, such as spinach, soy, and eggplant.