10-oxo-15-trimethylsilanyl-pentadec-14-yonic acid methyl ester | 1262788-53-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 10-oxo-15-trimethylsilanyl-pentadec-14-yonic acid methyl ester
• CAS: 1262788-53-3
• 化学式: C₁₉H₃₄O₃Si
• 分子量: 338.563
• InChiKey: RQWNPLMMSMYCKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23.0
• 可旋转键数：
  12.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  10-oxo-15-trimethylsilanyl-pentadec-14-yonic acid methyl ester 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 生成 Pentadec-14-in-saeure
  参考文献：
  名称：

  Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases

  摘要：

  SM is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling, and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase (SMS) 1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE, whereas a closely related enzyme, sphingomyelin synthase-related protein (SMSr)/SAMD8, acts as a monofunctional CPE synthase in the endoplasmatic reticulum. Using domain swapping and site-directed mutagenesis on enzymes expressed in defined lipid environments, we here identified structural determinants that mediate head group selectivity of SMS family members. Notably, a single residue adjacent to the catalytic histidine in the third exoplasmic loop profoundly influenced enzyme specificity, with glutamic acid permitting SMS-catalyzed CPE production and aspartic acid confining the enzyme to produce SM. An exchange of exoplasmic residues with SMSr proved sufficient to convert SMS1 into a bulk CPE synthase. This allowed us to establish mammalian cells that produce CPE rather than SM as the principal phosphosphingolipid and provide a model of the molecular interactions that impart catalytic specificity among SMS enzymes.-Kol, M., R. Panatala, M. Nordmann, L. Swart, L. van Suijlekom, B. Cabukusta, A. Hilderink, T. Grabietz, J. G. M. Mina, P. Somerharju, S. Korneev, F. G. Tafesse, and J. C. M. Holthuis. Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases.

  DOI：

  10.1194/jlr.m068692
• 作为产物：
  描述：

  10-氯-10-氧代癸酸甲酯 、 (5-氯-1-戊炔基)三甲基硅烷 在 magnesium 作用下， 以 乙醚 为溶剂， 生成 10-oxo-15-trimethylsilanyl-pentadec-14-yonic acid methyl ester
  参考文献：
  名称：

  Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases

  摘要：

  SM is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling, and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase (SMS) 1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE, whereas a closely related enzyme, sphingomyelin synthase-related protein (SMSr)/SAMD8, acts as a monofunctional CPE synthase in the endoplasmatic reticulum. Using domain swapping and site-directed mutagenesis on enzymes expressed in defined lipid environments, we here identified structural determinants that mediate head group selectivity of SMS family members. Notably, a single residue adjacent to the catalytic histidine in the third exoplasmic loop profoundly influenced enzyme specificity, with glutamic acid permitting SMS-catalyzed CPE production and aspartic acid confining the enzyme to produce SM. An exchange of exoplasmic residues with SMSr proved sufficient to convert SMS1 into a bulk CPE synthase. This allowed us to establish mammalian cells that produce CPE rather than SM as the principal phosphosphingolipid and provide a model of the molecular interactions that impart catalytic specificity among SMS enzymes.-Kol, M., R. Panatala, M. Nordmann, L. Swart, L. van Suijlekom, B. Cabukusta, A. Hilderink, T. Grabietz, J. G. M. Mina, P. Somerharju, S. Korneev, F. G. Tafesse, and J. C. M. Holthuis. Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases.

  DOI：

  10.1194/jlr.m068692

文献信息

• In Vivo Profiling and Visualization of Cellular Protein-Lipid Interactions Using Bifunctional Fatty Acids
  作者：Per Haberkant、Reinout Raijmakers、Marjolein Wildwater、Timo Sachsenheimer、Britta Brügger、Kenji Maeda、Martin Houweling、Anne-Claude Gavin、Carsten Schultz、Gerrit van Meer、Albert J. R. Heck、Joost C. M. Holthuis

  DOI：10.1002/anie.201210178

  日期：2013.4.2

  Bifunctional lipid technology: Cells convert externally added photoactivatable and “clickable” fatty acids into a variety of bifunctional phospholipids that can be covalently linked to their protein‐binding partners by irradiation with UV light. Derivatization of the clickable group with a reporter molecule makes it possible to identify and image the lipid‐bound proteins in situ (see scheme).

  双功能脂质技术：细胞将外部添加的可光活化和“可点击”的脂肪酸转化为多种双功能磷脂，这些双功能磷脂可以通过紫外线照射与它们的蛋白结合伴侣共价连接。用报道分子对可点击基团进行衍生化使得可以原位鉴定和成像脂质结合蛋白（参见方案）。