(S)-1-O-hexadecyl-3-O-benzyl-glycero-2-phosphocholine | 853997-34-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-1-O-hexadecyl-3-O-benzyl-glycero-2-phosphocholine
• 英文别名: 1-O-Hexadecyl-3-O-benzyl-sn-glycero-2-phosphocholine；[(2S)-1-hexadecoxy-3-phenylmethoxypropan-2-yl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 853997-34-9
• 化学式: C₃₁H₅₈NO₆P
• 分子量: 571.778
• InChiKey: HCOXBFSHNGCDQB-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.28
• 重原子数：
  39.0
• 可旋转键数：
  27.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  77.05
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-1-O-hexadecyl-3-O-benzyl-glycero-2-phosphocholine 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 以100%的产率得到(S)-1-O-hexadecyl-3-lyso-glycero-2-phosphocholine
  参考文献：
  名称：

  Secretory Phospholipase A₂ Hydrolysis of Phospholipid Analogues Is Dependent on Water Accessibility to the Active Site

  摘要：

  A new and unnatural type of phospholipids with the head group attached to the 2-position of the glycerol backbone has been synthesized and shown to be a good substrate for secretory phospholipase A(2) (sPLA(2)). To investigate the unexpected sPLA(2) activity, we have compared three different phospholipids by using fluorescence techniques and HPLC, namely: (R)-1,2-dipalmitoyl-glycero-3-phosphocholine (hereafter referred to as 1R), (R)-1-O-hexadecyl-2-palmitoyl-glycero-3-phoshocholine (2R), and (S)-1-O-hexadecyl-3-palmitoyl-glycero-2-phosphocholine (3S). Furthermore, to understand the underlying mechanisms for the observed differences, we have performed molecular dynamics simulations to clarify on a structural level the substrate specificity of sPLA(2) toward phospholipid analogues with their head groups in the 2-position of the glycerol backbone. We have studied the lipids above 1R, 2R, and 3S as well as their enantiomers 1S, 2S, and 3R. In the simulations of sPLA(2)-1S and sPLA(2)-3R, structural distortion in the binding cleft induced by the phospholipids showed that these are not substrates for sPLA(2). In the case of the phospholipids 1R, 2R, and 3S, our simulations revealed that the difference observed experimentally in sPLA(2) activity might be caused by reduced access of water molecules to the active site. We have monitored the number of water molecules that enter the active site region for the different sPLA(2)-phospholipid complexes and found that the probability of a water molecule reaching the correct position such that hydrolysis can occur is reduced for the unnatural lipids. The relative water count follows 1R > 2R > 3S. This is in good agreement with experimental data that indicate the same trend for sPLA(2) activity: 1R > 2R > 3S.

  DOI：

  10.1021/ja067755b
• 作为产物：
  描述：

  1-十六烷醇 在 sodium hydride 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (S)-1-O-hexadecyl-3-O-benzyl-glycero-2-phosphocholine
  参考文献：
  名称：

  Secretory Phospholipase A₂ Hydrolysis of Phospholipid Analogues Is Dependent on Water Accessibility to the Active Site

  摘要：

  A new and unnatural type of phospholipids with the head group attached to the 2-position of the glycerol backbone has been synthesized and shown to be a good substrate for secretory phospholipase A(2) (sPLA(2)). To investigate the unexpected sPLA(2) activity, we have compared three different phospholipids by using fluorescence techniques and HPLC, namely: (R)-1,2-dipalmitoyl-glycero-3-phosphocholine (hereafter referred to as 1R), (R)-1-O-hexadecyl-2-palmitoyl-glycero-3-phoshocholine (2R), and (S)-1-O-hexadecyl-3-palmitoyl-glycero-2-phosphocholine (3S). Furthermore, to understand the underlying mechanisms for the observed differences, we have performed molecular dynamics simulations to clarify on a structural level the substrate specificity of sPLA(2) toward phospholipid analogues with their head groups in the 2-position of the glycerol backbone. We have studied the lipids above 1R, 2R, and 3S as well as their enantiomers 1S, 2S, and 3R. In the simulations of sPLA(2)-1S and sPLA(2)-3R, structural distortion in the binding cleft induced by the phospholipids showed that these are not substrates for sPLA(2). In the case of the phospholipids 1R, 2R, and 3S, our simulations revealed that the difference observed experimentally in sPLA(2) activity might be caused by reduced access of water molecules to the active site. We have monitored the number of water molecules that enter the active site region for the different sPLA(2)-phospholipid complexes and found that the probability of a water molecule reaching the correct position such that hydrolysis can occur is reduced for the unnatural lipids. The relative water count follows 1R > 2R > 3S. This is in good agreement with experimental data that indicate the same trend for sPLA(2) activity: 1R > 2R > 3S.

  DOI：

  10.1021/ja067755b

文献信息

• WO2006/48017
  申请人：——

  公开号：——

  公开（公告）日：——