[(3S)-5-ethoxy-3-[[(2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]amino]hexanoyl]amino]-2,5-dioxopentyl] 2,6-dimethylbenzoate | 921771-34-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(3S)-5-ethoxy-3-[[(2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]amino]hexanoyl]amino]-2,5-dioxopentyl] 2,6-dimethylbenzoate
• CAS: 921771-34-8
• 化学式: C₄₄H₆₂N₄O₁₃
• 分子量: 854.995
• InChiKey: OZBJTJNMORAOKX-ZDCRTTOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  61
• 可旋转键数：
  29
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  231
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  [(3S)-5-ethoxy-3-[[(2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]amino]hexanoyl]amino]-2,5-dioxopentyl] 2,6-dimethylbenzoate 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 (4S)-5-[[(2S)-6-[5-[(3aS,4S,6aR)-2-amino-3a,4,6,6a-tetrahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoylamino]-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
• 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 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以80%的产率得到[(3S)-5-ethoxy-3-[[(2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoyl]amino]hexanoyl]amino]-2,5-dioxopentyl] 2,6-dimethylbenzoate
  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