H-D-Val-D-Val-D-Ile-D-Ala-OH | 1351638-83-9

• 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: H-D-Val-D-Val-D-Ile-D-Ala-OH
• 英文别名: (2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]propanoic acid
• CAS: 1351638-83-9
• 化学式: C₁₉H₃₆N₄O₅
• 分子量: 400.519
• InChiKey: KCPRUEOKTJVOSP-KJWHEZOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  151
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Fmoc-D-丙氨酸 、 Fmoc-D-缬氨酸 、 Fmoc-D-异亮氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.13h， 生成 H-D-Val-D-Val-D-Ile-D-Ala-OH
  参考文献：
  名称：

  C-Terminal Tetrapeptides Inhibit Aβ42-Induced Neurotoxicity Primarily through Specific Interaction at the N-Terminus of Aβ42

  摘要：

  Inhibition of amyloid beta-protein (A beta)-induced toxicity is a promising therapeutic strategy for Alzheimer's disease (AD). Previously, we reported that the C-terminal tetrapeptide A beta(39-42) is a potent inhibitor of neurotoxicity caused by A beta 42, the form of A beta most closely associated with AD. Here, initial structure activity relationship studies identified key structural requirements, including chirality, side-chain structure, and a free N-terminus, which control A beta(39-42) inhibitory activity. To elucidate the binding site(s) of A beta(39-42) on A beta 42, we used intrinsic tyrosine (Y) fluorescence and solution-state NMR. The data suggest that A beta(39-42) binds at several sites, of which the predominant one is located in the N-terminus of A beta 42, in agreement with recent modeling predictions. Thus, despite the small size of A beta(39-42) and the hydrophobic, aliphatic nature of all four side-chains, the interaction of A beta(39-42) with A beta 42 is controlled by specific intermolecular contacts requiring a combination of hydrophobic and electrostatic interactions and a particular stereochemistry.

  DOI：

  10.1021/jm200982p

文献信息

• C-Terminal Tetrapeptides Inhibit Aβ42-Induced Neurotoxicity Primarily through Specific Interaction at the N-Terminus of Aβ42
  作者：Huiyuan Li、Zhenming Du、Dahabada H. J. Lopes、Erica A. Fradinger、Chunyu Wang、Gal Bitan

  DOI：10.1021/jm200982p

  日期：2011.12.22

  Inhibition of amyloid beta-protein (A beta)-induced toxicity is a promising therapeutic strategy for Alzheimer's disease (AD). Previously, we reported that the C-terminal tetrapeptide A beta(39-42) is a potent inhibitor of neurotoxicity caused by A beta 42, the form of A beta most closely associated with AD. Here, initial structure activity relationship studies identified key structural requirements, including chirality, side-chain structure, and a free N-terminus, which control A beta(39-42) inhibitory activity. To elucidate the binding site(s) of A beta(39-42) on A beta 42, we used intrinsic tyrosine (Y) fluorescence and solution-state NMR. The data suggest that A beta(39-42) binds at several sites, of which the predominant one is located in the N-terminus of A beta 42, in agreement with recent modeling predictions. Thus, despite the small size of A beta(39-42) and the hydrophobic, aliphatic nature of all four side-chains, the interaction of A beta(39-42) with A beta 42 is controlled by specific intermolecular contacts requiring a combination of hydrophobic and electrostatic interactions and a particular stereochemistry.