globotriaosyl-E-ceramide | 82005-99-0

• 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: globotriaosyl-E-ceramide
• 英文别名: 1-O-(α-Gal-4-β-Gal-4-β-Glc)ceramide d18:1/C24:0；alpha-D-Gal-(1->4)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1')-Cer(d18:1/24:0)；N-[(E,2S,3R)-1-[(2R,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-hydroxyoctadec-4-en-2-yl]tetracosanamide
• CAS: 82005-99-0
• 化学式: C₆₀H₁₁₃NO₁₈
• 分子量: 1136.55
• InChiKey: MRVRZXMLIKCXOT-SHLWWNIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  79
• 可旋转键数：
  47
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  307
• 氢给体数：
  12
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-(1-4)-O-(2,3,6-tri-O-acetyl-β-D-galactopyranosyl)-(1-4)-O-(2,3,6-tri-O-acetyl-β-D-glucopyranosyl)-(1-1)-(2S,3R,4E)-3-O-benzoyl-2-N-tetracosanoylsphingenine 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 以83%的产率得到globotriaosyl-E-ceramide
  参考文献：
  名称：

  globotriaosyl-E和Z-神经酰胺和异globotriaosyl-E-神经酰胺的全合成

  摘要：

  O-α-D-吡喃半乳糖基-（1 ---- 4）-O-β-D-吡喃半乳糖基-（1 ---- 4）-O-β-D-吡喃葡萄糖基-（1-的立体选择性全合成--- 1）-N-十四烷酰基-[2S，3R，4E（和4Z）]-鞘氨醇和O-α-D-吡喃半乳糖基-（1 ---- 3）-O-β-D-吡喃半乳糖基-（通过使用O-（2,3）可实现1 ---- 4）-O-β-D-吡喃葡萄糖基-（1 ---- 1）-N-十四烷酰基-（2S，3R，4E）-斯宾碱，4,6-四-O-乙酰基-α-D-吡喃半乳糖基）-（1 ---- 4）-O-（2,3,6-三-O-乙酰基-β-D-吡喃半乳糖基）-（ 1 ---- 4）-2,3,6-三-O-乙酰基-α-D-吡喃葡萄糖基三氯乙酰亚氨酸酯，O-（2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基） -（1 ---- 4）-O-（2,3,6-三-O-乙酰基-β-D-吡喃半乳糖基）-（1

  DOI：

  10.1016/0008-6215(87)80181-7

文献信息

• Influence of Gb3 glycosphingolipids differing in their fatty acid chain on the phase behaviour of solid supported membranes: chemical syntheses and impact of Shiga toxin binding
  作者：Ole M. Schütte、Annika Ries、Alexander Orth、Lukas J. Patalag、Winfried Römer、Claudia Steinem、Daniel B. Werz

  DOI：10.1039/c4sc01290a

  日期：——

  The Shiga toxin B subunit (STxB), which is involved in cell membrane attachment and trafficking of Shiga holotoxin, binds specifically to the glycosphingolipid Gb3. In biological membranes, Gb3 glycosphingolipids differ in their fatty acid composition and there is strong evidence that the fatty acid alters the binding behaviour of STxB as well as the intracellular routing of the Shiga toxin/Gb3 complex. To analyse the binding of STxB to different Gb3s, we chemically synthesized saturated, unsaturated, α-hydroxylated Gb3s and a combination thereof, all based on a C24-fatty acid chain starting from monosaccharide building blocks, sphingosine and the respective fatty acids. These chemically well-defined Gb3s were inserted into solid supported phase-separated lipid bilayers composed of DOPC/sphingomyelin/cholesterol as a simple mimetic of the outer leaflet of animal cell membranes. By fluorescence- and atomic force microscopy the phase behaviour of the bilayer as well as the lateral organization of bound STxB were analysed. The fatty acid of Gb3 significantly alters the ratio between the ordered and disordered phase and induces a third intermediate phase in the presence of unsaturated Gb3. The lateral organization of STxB on the membranes varies significantly. While STxB attached to membranes with Gb3s with saturated fatty acids forms protein clusters, it is more homogeneously bound to membranes containing unsaturated Gb3s. Large interphase lipid redistribution is observed for α-hydroxylated Gb3 doped membranes. Our results clearly demonstrate that the fatty acid of Gb3 strongly influences the lateral organization of STxB on the membrane and impacts the overall membrane organization of phase-separated lipid membranes.

  志贺毒素B亚基（STxB）参与细胞膜附着和志贺毒素的转运，特异性地结合到糖神经酰胺Gb3上。在生物膜中，Gb3糖神经酰胺的脂肪酸组成不同，有强有力的证据表明脂肪酸改变STxB的结合行为以及志贺毒素/Gb3复合物的细胞内运输途径。为了分析STxB与不同Gb3的结合，我们化学合成了饱和、不饱和、α-羟基化的Gb3及其组合，所有这些都基于从单糖构建块、鞘氨醇和相应的脂肪酸开始的C24脂肪酸链。这些化学上定义明确的Gb3被插入到由DOPC/鞘磷脂/胆固醇组成的固相分离脂质双层中，作为动物细胞膜外叶的简单模拟物。通过荧光显微镜和原子力显微镜分析了双层的相行为以及STxB结合的侧向组织。Gb3的脂肪酸显著改变了有序和无序相的比例，并在存在不饱和Gb3的情况下诱导了第三种中间相。STxB在膜上的侧向组织显著变化。当STxB附着在含有饱和脂肪酸Gb3的膜上时形成蛋白质簇，它更均匀地结合到含有不饱和Gb3的膜上。观察到α-羟基化Gb3掺杂膜的大相间脂质重分布。我们的结果清楚地表明，Gb3的脂肪酸强烈影响STxB在膜上的侧向组织，并影响相分离脂质膜的整体膜组织。
• Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease
  作者：Satoshi Ishii、Atsumi Taguchi、Nozomu Okino、Makoto Ito、Hiroki Maruyama

  DOI：10.1074/jbc.ra120.012665

  日期：2020.4

  Fabry disease is a heritable lipid disorder caused by the low activity of ?-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(?2) containing the lyso-Gb3(?2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(?2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease.
• Total synthesis of globotriaosyl-E and Z-ceramides and isoglobotriaosyl-E-ceramide
  作者：Katsuya Koike、Mamoru Sugimoto、Susumu Sato、Yukishige Ito、Yoshiaki Nakahara、Tomoya Ogawa

  DOI：10.1016/0008-6215(87)80181-7

  日期：1987.6

  Stereoselective, total synthesis of O-alpha-D-galactopyranosyl-(1----4) -O-beta-D-galactopyranosyl-(1----4)-O-beta-D-glucopyranosyl-(1----1)-N -tetracosanoyl-[2S,3R,4E (and 4Z)]-sphingenine and O-alpha-D -galactopyranosyl-(1----3)-O-beta-D-galactopyranosyl-(1----4)-O-beta-D -glucopyranosyl-(1----1)-N-tetracosanoyl-(2S,3R,4E)-sphin gen ine was achieved by using O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl)

  O-α-D-吡喃半乳糖基-（1 ---- 4）-O-β-D-吡喃半乳糖基-（1 ---- 4）-O-β-D-吡喃葡萄糖基-（1-的立体选择性全合成--- 1）-N-十四烷酰基-[2S，3R，4E（和4Z）]-鞘氨醇和O-α-D-吡喃半乳糖基-（1 ---- 3）-O-β-D-吡喃半乳糖基-（通过使用O-（2,3）可实现1 ---- 4）-O-β-D-吡喃葡萄糖基-（1 ---- 1）-N-十四烷酰基-（2S，3R，4E）-斯宾碱，4,6-四-O-乙酰基-α-D-吡喃半乳糖基）-（1 ---- 4）-O-（2,3,6-三-O-乙酰基-β-D-吡喃半乳糖基）-（ 1 ---- 4）-2,3,6-三-O-乙酰基-α-D-吡喃葡萄糖基三氯乙酰亚氨酸酯，O-（2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基） -（1 ---- 4）-O-（2,3,6-三-O-乙酰基-β-D-吡喃半乳糖基）-（1