3-[(E)-[5-(2,2-dimethylpropanoyloxymethyl)-5-(hydroxymethyl)-2-oxooxolan-3-ylidene]methyl]benzoic acid | 1597428-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[(E)-[5-(2,2-dimethylpropanoyloxymethyl)-5-(hydroxymethyl)-2-oxooxolan-3-ylidene]methyl]benzoic acid
• CAS: 1597428-77-7
• 化学式: C₁₉H₂₂O₇
• 分子量: 362.379
• InChiKey: HNXGPIHBAOCZTI-RIYZIHGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-羧基苯甲醛 在 4-二甲氨基吡啶 、 ammonium cerium (IV) nitrate 、 三氯化硼 、 甲基磺酰氯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.0h， 生成 3-[(E)-[5-(2,2-dimethylpropanoyloxymethyl)-5-(hydroxymethyl)-2-oxooxolan-3-ylidene]methyl]benzoic acid
  参考文献：
  名称：

  Diacylglycerol Lactones Targeting the Structural Features That Distinguish the Atypical C1 Domains of Protein Kinase C ζ and ι from Typical C1 Domains

  摘要：

  To explore the feasibility of developing ligands targeted to the atypical C1 domains of protein kinase C zeta and iota, we have prepared diacylglycerol lactones substituted with hydrophilic groups on their side chains, which potentially could interact with the arginine residues that distinguish the atypical C1 domains of PKC zeta and PKC?iota from typical C1 domains, and we have measured their binding to mutated versions of the C1b domain of PKC delta that incorporate one or more of these arginine residues. The most selective of the diacylglycerol lactones showed only a 10-fold reduction in binding affinity with the triple arginine mutant (N7R/S10R/L20R) compared to the wild-type, whereas phorbol 12,13-dibutyrate showed a 6000-fold loss of affinity. Molecular modeling confirms that these ligands are indeed able to interact with the arginine residues. Our results show that dramatic changes in selectivity can be obtained through appropriate substitution of diacylglycerol lactones.

  DOI：

  10.1021/jm500165n

文献信息

• Diacylglycerol Lactones Targeting the Structural Features That Distinguish the Atypical C1 Domains of Protein Kinase C ζ and ι from Typical C1 Domains
  作者：Yongmei Pu、Ji-Hye Kang、Dina M. Sigano、Megan L. Peach、Nancy E. Lewin、Victor E. Marquez、Peter M. Blumberg

  DOI：10.1021/jm500165n

  日期：2014.5.8

  To explore the feasibility of developing ligands targeted to the atypical C1 domains of protein kinase C zeta and iota, we have prepared diacylglycerol lactones substituted with hydrophilic groups on their side chains, which potentially could interact with the arginine residues that distinguish the atypical C1 domains of PKC zeta and PKC?iota from typical C1 domains, and we have measured their binding to mutated versions of the C1b domain of PKC delta that incorporate one or more of these arginine residues. The most selective of the diacylglycerol lactones showed only a 10-fold reduction in binding affinity with the triple arginine mutant (N7R/S10R/L20R) compared to the wild-type, whereas phorbol 12,13-dibutyrate showed a 6000-fold loss of affinity. Molecular modeling confirms that these ligands are indeed able to interact with the arginine residues. Our results show that dramatic changes in selectivity can be obtained through appropriate substitution of diacylglycerol lactones.