| 1204085-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• CAS: 1204085-63-1
• 化学式: C₆H₁₅N*C₇₅H₁₁₃N₆O₁₆PSSi₃
• 分子量: 1603.24
• InChiKey: SUGNXOXYSBZDHY-TUNHGBNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.3
• 重原子数：
  109.0
• 可旋转键数：
  48.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  271.08
• 氢给体数：
  5.0
• 氢受体数：
  19.0

反应信息

• 作为反应物：
  描述：

  在 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 碳酸氢钠 作用下， 以 乙腈 、 水 为溶剂， 反应 2.0h， 以2.2 mg的产率得到N,N-diethylethanaminium (1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-trihydroxy-1-((2S,3S)-3-[(4-(2-[2-((1-[2-(2-([5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]amino)ethoxy)ethyl]-1H-1,2,3-triazol-4-yl)methoxy)ethoxy]ethoxy)benzyl)oxy]-6-oxo-3,6-dihydro-2H-pyran-2-yl)-3-methyltrideca-1,7,9,11-tetraen-4-yl hydrogen phosphate
  参考文献：
  名称：

  Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells

  摘要：

  Fostriecin is a phosphate monoester with excellent antitumor activity against mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. This compound has been predicted to covalently bind to the Cys269 residue of the PP2A catalytic subunit (PP2Ac) at the alpha,beta-unsaturated lactone via a conjugate addition reaction. However, this binding has not yet been experimentally proven. To confirm such binding, we synthesized biotin-labeled fostriecin (bio-Fos), which has an inhibitory activity against the proliferation of mouse leukemia cells. We showed that fostriecin directly binds to PP2Ac in HeLa S3 cells by pull-down assays using bio-Fos. Moreover, we directly demonstrated that fostriecin covalently binds to the Cys269 residue of PP2Ac by matrix assisted laser desorption/ionization time-of-flight mass spectrometry analysis. From these results, the inhibitory mechanism of fostriecin on PP2A activity is discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.050
• 作为产物：
  描述：

  、 三乙胺 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells

  摘要：

  Fostriecin is a phosphate monoester with excellent antitumor activity against mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. This compound has been predicted to covalently bind to the Cys269 residue of the PP2A catalytic subunit (PP2Ac) at the alpha,beta-unsaturated lactone via a conjugate addition reaction. However, this binding has not yet been experimentally proven. To confirm such binding, we synthesized biotin-labeled fostriecin (bio-Fos), which has an inhibitory activity against the proliferation of mouse leukemia cells. We showed that fostriecin directly binds to PP2Ac in HeLa S3 cells by pull-down assays using bio-Fos. Moreover, we directly demonstrated that fostriecin covalently binds to the Cys269 residue of PP2Ac by matrix assisted laser desorption/ionization time-of-flight mass spectrometry analysis. From these results, the inhibitory mechanism of fostriecin on PP2A activity is discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.050