(4S)-4-amino-5-[[(2S)-1-[[(2S)-4-amino-1-[[(4S,5S,7S)-7-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-5-hydroxy-2,8-dimethylnonan-4-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid | 1292778-93-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (4S)-4-amino-5-[[(2S)-1-[[(2S)-4-amino-1-[[(4S,5S,7S)-7-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-5-hydroxy-2,8-dimethylnonan-4-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
• CAS: 1292778-93-8
• 化学式: C₄₃H₆₈N₈O₁₄
• 分子量: 921.058
• InChiKey: AQVQJKSMBFXSEE-PFCVTPPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  65
• 可旋转键数：
  30
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  376
• 氢给体数：
  12
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  Fmoc-Phe-Wang resin 、 Fmoc-L-缬氨酸 、 Fmoc-L-丙氨酸 、 4(S)-<(tert-butyldimethylsilyl)oxy>-5(S)-<(tert-butyloxycarbonyl)amino>-2(S)-isopropyl-7-methyloctanoic acid 、 Fmoc-O-叔丁基-L-谷氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 在 哌啶 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 1-甲基吡咯烷 为溶剂， 反应 0.25h， 生成 (4S)-4-amino-5-[[(2S)-1-[[(2S)-4-amino-1-[[(4S,5S,7S)-7-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-5-hydroxy-2,8-dimethylnonan-4-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  On a Possible Neutral Charge State for the Catalytic Dyad in β-Secretase When Bound to Hydroxyethylene Transition State Analogue Inhibitors

  摘要：

  beta-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients Our previous results using a combination of surface plasmon resonance experiments with molecular Modeling calculations: suggested that the Asp dyad in beta-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.

  DOI：

  10.1021/jm101568y

文献信息

• On a Possible Neutral Charge State for the Catalytic Dyad in β-Secretase When Bound to Hydroxyethylene Transition State Analogue Inhibitors
  作者：Fredy Sussman、José M. Otero、M. Carmen Villaverde、Marian Castro、José L. Domínguez、Lucía González-Louro、Ramón J. Estévez、J. Carlos Estévez

  DOI：10.1021/jm101568y

  日期：2011.4.28

  beta-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients Our previous results using a combination of surface plasmon resonance experiments with molecular Modeling calculations: suggested that the Asp dyad in beta-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.