(4S)-5-[[(2S)-6-amino-1-[[(2S)-1-carboxy-4-(2,6-dimethylbenzoyl)oxy-3-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid | 921771-35-9

• 分子结构分类: 有机化合物
• 英文名称: (4S)-5-[[(2S)-6-amino-1-[[(2S)-1-carboxy-4-(2,6-dimethylbenzoyl)oxy-3-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 921771-35-9
• 化学式: C₃₃H₄₂N₄O₁₁
• 分子量: 670.717
• InChiKey: HQXQTTNTONQGCC-SDHOMARFSA-N

物化性质

• 沸点：
  993.4±65.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  48
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  241
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (4S)-5-[[(2S)-6-amino-1-[[(2S)-1-carboxy-4-(2,6-dimethylbenzoyl)oxy-3-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid 、 (+)生物素-N-琥珀酰亚胺基酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以75%的产率得到2,6-dimethyl-benzoic acid (S)-3-{(S)-2-((S)-2-benzyloxycarbonylamino-4-carboxy-butyrylamino)-6-[5-((3aS,4S,6aR)-2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoylamino}-4-carboxy-2-oxo-butyl ester
  参考文献：
  名称：

  Synthesis of Novel Caspase Inhibitors for Characterization of the Active Caspase Proteome in Vitro and in Vivo

  摘要：

  Caspases are cysteine proteases that are essential for cytokine maturation and apoptosis. To facilitate the dissection of caspase function in vitro and in vivo, we have synthesized irreversible caspase inhibitors with biotin attached via linker arms of various lengths (12a-d) and a 2,4-dinitrophenyl labeled inhibitor (13). Affinity labeling of apoptotic extracts followed by blotting reveals that these affinity probes detect active caspases. Using the strong affinity of avidin for biotin, we have isolated affinity-labeled caspase 6 from apoptotic cytosolic extracts of cells overexpressing procaspase 6 by treatment with 12c, which contains biotin attached to the N-epsilon-lysine of the inhibitor by a 22.5 A linker arm, followed by affinity purification on monomeric avidin-sepharose beads. Compound 13 has proven sufficiently cell permeable to rescue cells from apoptotic execution. These novel caspase inhibitors should provide powerful probes for the study of the active caspase proteome during apoptosis both in vitro and in vivo.

  DOI：

  10.1021/jm060385h
• 作为产物：
  描述：

  [(2R,3S)-5-ethoxy-2-hydroxy-3-[[(2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]amino]hexanoyl]amino]-5-oxopentyl] 2,6-dimethylbenzoate 在 戴斯-马丁氧化剂 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 (4S)-5-[[(2S)-6-amino-1-[[(2S)-1-carboxy-4-(2,6-dimethylbenzoyl)oxy-3-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid
  参考文献：
  名称：

  Synthesis of Novel Caspase Inhibitors for Characterization of the Active Caspase Proteome in Vitro and in Vivo

  摘要：

  Caspases are cysteine proteases that are essential for cytokine maturation and apoptosis. To facilitate the dissection of caspase function in vitro and in vivo, we have synthesized irreversible caspase inhibitors with biotin attached via linker arms of various lengths (12a-d) and a 2,4-dinitrophenyl labeled inhibitor (13). Affinity labeling of apoptotic extracts followed by blotting reveals that these affinity probes detect active caspases. Using the strong affinity of avidin for biotin, we have isolated affinity-labeled caspase 6 from apoptotic cytosolic extracts of cells overexpressing procaspase 6 by treatment with 12c, which contains biotin attached to the N-epsilon-lysine of the inhibitor by a 22.5 A linker arm, followed by affinity purification on monomeric avidin-sepharose beads. Compound 13 has proven sufficiently cell permeable to rescue cells from apoptotic execution. These novel caspase inhibitors should provide powerful probes for the study of the active caspase proteome during apoptosis both in vitro and in vivo.

  DOI：

  10.1021/jm060385h