(2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-(2,6,6-trimethyl-3-oxocyclohex-1-enyl)nona-2,4,6,8-tetraenoate | 1225383-35-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-(2,6,6-trimethyl-3-oxocyclohex-1-enyl)nona-2,4,6,8-tetraenoate
• CAS: 1225383-35-6
• 化学式: C₂₃H₂₉NO₃
• 分子量: 367.488
• InChiKey: HHQWFXTVDOZAFU-VKGWHYSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.15
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  67.16
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-(2,6,6-trimethyl-3-oxocyclohex-1-enyl)nona-2,4,6,8-tetraenoate 、 2-(氨基氧基)乙酸 以 吡啶 为溶剂， 反应 17.0h， 以100%的产率得到(2E,4E,6E,8E)-2-cyanoethyl 9-((E)-3-(2-hydroxy-2-oxoethoxyimino)-2,6,6-trimethylcyclohex-1-enyl)-3,7-dimethylnona-2,4,6,8-tetraenoate
  参考文献：
  名称：

  Protein Knockdown Using Methyl Bestatin−Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins

  摘要：

  Induction of selective degradation of target proteins by small molecules (protein knockdown) would be useful for biological research and treatment of various diseases. To achieve protein knockdown, we utilized the ubiquitin ligase activity of cellular inhibitor of apoptosis protein 1 (cIAP1), which is activated by methyl bestatin (MeBS, 2). We speculated that formation of an artificial (nonphysiological) complex of cIAP1 and a target protein would be induced by a hybrid molecule consisting of MeBS (2) linked to a ligand of the target protein, and this would lead to cIAP1-mediated ubiquitination and subsequent proteasomal degradation of the target protein. To verify this hypothesis, we focused on cellular retinoic acid-binding proteins (CRABP-I and -II) and designed hybrid molecules (compounds 4) consisting of MeBS (2) coupled via spacers of various lengths to all-trans retinoic acid (ATRA, 3), a ligand of CRABPs. Compounds 4 induced selective loss of CRABP-I and -II proteins in cells. We confirmed that 4b induced formation of a complex of cIAP1 and CRABP-II in vitro and induced proteasomal degradation of CRABP-II in cells. When neuroblastoma IMR-32 cells were treated with 4b, the level of CRABP-II was reduced and cell migration was inhibited, suggesting potential value of CRABP-II-targeting therapy for controlling tumor metastasis. Our results indicate that 4b possesses sufficient activity, permeability, and stability in cells to be employed in cellular assays. Hybrid molecules such as 4 should be useful not only as chemical tools for studying the biological/physiological functions of CRABPs but also as candidate therapeutic agents targeting CRABPs.

  DOI：

  10.1021/ja100691p
• 作为产物：
  描述：

  (2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoate 在 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 以36%的产率得到(2E,4E,6E,8E)-2-cyanoethyl 3,7-dimethyl-9-(2,6,6-trimethyl-3-oxocyclohex-1-enyl)nona-2,4,6,8-tetraenoate
  参考文献：
  名称：

  Protein Knockdown Using Methyl Bestatin−Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins

  摘要：

  Induction of selective degradation of target proteins by small molecules (protein knockdown) would be useful for biological research and treatment of various diseases. To achieve protein knockdown, we utilized the ubiquitin ligase activity of cellular inhibitor of apoptosis protein 1 (cIAP1), which is activated by methyl bestatin (MeBS, 2). We speculated that formation of an artificial (nonphysiological) complex of cIAP1 and a target protein would be induced by a hybrid molecule consisting of MeBS (2) linked to a ligand of the target protein, and this would lead to cIAP1-mediated ubiquitination and subsequent proteasomal degradation of the target protein. To verify this hypothesis, we focused on cellular retinoic acid-binding proteins (CRABP-I and -II) and designed hybrid molecules (compounds 4) consisting of MeBS (2) coupled via spacers of various lengths to all-trans retinoic acid (ATRA, 3), a ligand of CRABPs. Compounds 4 induced selective loss of CRABP-I and -II proteins in cells. We confirmed that 4b induced formation of a complex of cIAP1 and CRABP-II in vitro and induced proteasomal degradation of CRABP-II in cells. When neuroblastoma IMR-32 cells were treated with 4b, the level of CRABP-II was reduced and cell migration was inhibited, suggesting potential value of CRABP-II-targeting therapy for controlling tumor metastasis. Our results indicate that 4b possesses sufficient activity, permeability, and stability in cells to be employed in cellular assays. Hybrid molecules such as 4 should be useful not only as chemical tools for studying the biological/physiological functions of CRABPs but also as candidate therapeutic agents targeting CRABPs.

  DOI：

  10.1021/ja100691p