N-月桂酰-D-赤型-鞘氨酰磷酰胆碱 | 474923-21-2

• 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-月桂酰-D-赤型-鞘氨酰磷酰胆碱
• 英文名称: N-lauroyl-D-erythro-sphingosyl phosphorylcholine
• 英文别名: N-dodecanoyl-D-erythro-sphingosylphosphorylcholine；N-(dodecanoyl)-sphing-4-enine-1-phosphocholine；[(E,2S,3R)-2-(dodecanoylamino)-3-hydroxyoctadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 474923-21-2
• 化学式: C₃₅H₇₁N₂O₆P
• 分子量: 646.932
• InChiKey: HZCLJRFPXMKWHR-FEBLJDHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.1
• 重原子数：
  44
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-月桂酰-D-赤型-鞘氨酰磷酰胆碱 生成 胆碱 、 N-lauroyl-sphingosine-1,3-cyclophosphate(1-)
  参考文献：
  名称：

  Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders

  摘要：

  Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These enzymes convert sphingolipid and lysolipid substrates to cyclic phosphates by activating a hydroxyl nucleophile present in both classes of lipid. The most medically relevant substrates are thought to be sphingomyelin and/or lysophosphatidylcholine. To better understand the substrate preference of these toxins, we used P-31 NMR to compare the activity of three related but phylogenetically diverse sicariid toxins against a diverse panel of sphingolipid and lysolipid substrates. Two of the three showed significantly faster turnover of sphingolipids over lysolipids, and all three showed a strong preference for positively charged (choline and/or ethanolamine) over neutral (glycerol and serine) headgroups. Strikingly, however, the enzymes vary widely in their preference for choline, the headgroup of both sphingomyelin and lysophosphatidylcholine, versus ethanolamine. An enzyme from Sicarius terrosus showed a strong preference for ethanolamine overcholine, whereas two paralogous enzymes from Loxosceles arizonica either preferred choline or showed no significant preference. Intrigued by the novel substrate preference of the Sicarius enzyme, we solved its crystal structure at 2.1 angstrom resolution. The evolution of variable substrate specificity may help explain the reduced dermonecrotic potential of some natural toxin variants, because mammalian sphingolipids use primarily choline as a positively charged headgroup; it may also be relevant for sicariid predatory behavior, because ethanolamine-containing sphingolipids are common in insect prey.

  DOI：

  10.1074/jbc.m115.636951
• 作为产物：
  描述：

  dodecanoyl-AMP 、 D-赤藓-鞘氨醇磷酸胆碱 在 lithium chloride 作用下， 以 aq. buffer 为溶剂， 生成 N-月桂酰-D-赤型-鞘氨酰磷酰胆碱
  参考文献：
  名称：

  水中天然和益生元 1,2-氨基醇两亲物的化学选择性酯化

  摘要：

  在细胞中，大量的膜脂是通过极性头基与酰化剂（例如脂肪酰辅酶A）的酶促O-酰化形成的。尽管这种含酯的脂质似乎是地球上生命的必需品，但尚不清楚在生命起源时缺乏酶机制的情况下是否可以自发形成类似类型的脂质。两亲物在水中进行无酶酯化的例子很少，而且没有一个可以在生理 pH 值下使用生化相关酰化剂在水中发生的例子。在这里，我们报道了 Cu(II) 和其他几种过渡金属离子引导下的 1,2-氨基醇两亲物在水中发生意外的化学选择性 O-酰化。在含有 Cu(II) 离子的缓冲液中，将生物 1,2-氨基醇两亲物（例如鞘氨酰磷酰胆碱）与生化相关的酰化剂（即酰基腺苷酸和酰基辅酶 A）混合，可形成高选择性的 O-酰化产物。由此产生的 O-酰化鞘脂自组装成囊泡，其生物物理特性与由 N-酰基对应物形成的囊泡明显不同。我们还证明 Cu(II) 可以指导替代 1,2-氨基醇的 O-酰化，包括益生元相关的 1,2-氨基醇两亲

  DOI：

  10.1021/jacs.3c12038

文献信息

• Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders
  作者：Daniel M. Lajoie、Sue A. Roberts、Pamela A. Zobel-Thropp、Jared L. Delahaye、Vahe Bandarian、Greta J. Binford、Matthew H.J. Cordes

  DOI：10.1074/jbc.m115.636951

  日期：2015.4

  Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These enzymes convert sphingolipid and lysolipid substrates to cyclic phosphates by activating a hydroxyl nucleophile present in both classes of lipid. The most medically relevant substrates are thought to be sphingomyelin and/or lysophosphatidylcholine. To better understand the substrate preference of these toxins, we used P-31 NMR to compare the activity of three related but phylogenetically diverse sicariid toxins against a diverse panel of sphingolipid and lysolipid substrates. Two of the three showed significantly faster turnover of sphingolipids over lysolipids, and all three showed a strong preference for positively charged (choline and/or ethanolamine) over neutral (glycerol and serine) headgroups. Strikingly, however, the enzymes vary widely in their preference for choline, the headgroup of both sphingomyelin and lysophosphatidylcholine, versus ethanolamine. An enzyme from Sicarius terrosus showed a strong preference for ethanolamine overcholine, whereas two paralogous enzymes from Loxosceles arizonica either preferred choline or showed no significant preference. Intrigued by the novel substrate preference of the Sicarius enzyme, we solved its crystal structure at 2.1 angstrom resolution. The evolution of variable substrate specificity may help explain the reduced dermonecrotic potential of some natural toxin variants, because mammalian sphingolipids use primarily choline as a positively charged headgroup; it may also be relevant for sicariid predatory behavior, because ethanolamine-containing sphingolipids are common in insect prey.
• Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water
  作者：Ahanjit Bhattacharya、Lalita Tanwar、Alessandro Fracassi、Roberto J. Brea、Marta Salvador-Castell、Satyam Khanal、Sunil K. Sinha、Neal K. Devaraj

  DOI：10.1021/jacs.3c12038

  日期：2023.12.13

  enzyme-free esterification of amphiphiles in water and none that can occur in water at physiological pH using biochemically relevant acylating agents. Here we report the unexpected chemoselective O-acylation of 1,2-amino alcohol amphiphiles in water directed by Cu(II) and several other transition metal ions. In buffers containing Cu(II) ions, mixing biological 1,2-amino alcohol amphiphiles such as sphingosylphosphorylcholine

  在细胞中，大量的膜脂是通过极性头基与酰化剂（例如脂肪酰辅酶A）的酶促O-酰化形成的。尽管这种含酯的脂质似乎是地球上生命的必需品，但尚不清楚在生命起源时缺乏酶机制的情况下是否可以自发形成类似类型的脂质。两亲物在水中进行无酶酯化的例子很少，而且没有一个可以在生理 pH 值下使用生化相关酰化剂在水中发生的例子。在这里，我们报道了 Cu(II) 和其他几种过渡金属离子引导下的 1,2-氨基醇两亲物在水中发生意外的化学选择性 O-酰化。在含有 Cu(II) 离子的缓冲液中，将生物 1,2-氨基醇两亲物（例如鞘氨酰磷酰胆碱）与生化相关的酰化剂（即酰基腺苷酸和酰基辅酶 A）混合，可形成高选择性的 O-酰化产物。由此产生的 O-酰化鞘脂自组装成囊泡，其生物物理特性与由 N-酰基对应物形成的囊泡明显不同。我们还证明 Cu(II) 可以指导替代 1,2-氨基醇的 O-酰化，包括益生元相关的 1,2-氨基醇两亲