(S)-methyl 2-((S)-2-((S)-2-acetamidopropanamido)-6-(2-chloroacetamido)hexanamido)propanoate | 1245942-91-9

• 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: (S)-methyl 2-((S)-2-((S)-2-acetamidopropanamido)-6-(2-chloroacetamido)hexanamido)propanoate
• 英文别名: Ac-Ala-Lys(AcCl)-Ala-OMe；methyl (2S)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-6-[(2-chloroacetyl)amino]hexanoyl]amino]propanoate
• CAS: 1245942-91-9
• 化学式: C₁₇H₂₉ClN₄O₆
• 分子量: 420.893
• InChiKey: CLIQFSKAZWONHK-GVXVVHGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  28
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-methyl 2-((S)-2-((S)-2-acetamidopropanamido)-6-aminohexanamido)propanoate 、 氯乙酸 在 吡啶 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以17%的产率得到(S)-methyl 2-((S)-2-((S)-2-acetamidopropanamido)-6-(2-chloroacetamido)hexanamido)propanoate
  参考文献：
  名称：

  Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2

  摘要：

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.035

文献信息

• Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2
  作者：Tero Huhtiniemi、Tiina Suuronen、Maija Lahtela-Kakkonen、Tanja Bruijn、Sanna Jääskeläinen、Antti Poso、Antero Salminen、Jukka Leppänen、Elina Jarho

  DOI：10.1016/j.bmc.2010.06.035

  日期：2010.8

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.