(2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoic acid
• 化学式: C₂₇H₂₉ClNO₃Pol
• 分子量: 426.5
• InChiKey: BPOYFIVLVLAVNQ-XOBRGWDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chlorotrityl chloride polystyrene resin 、 (2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoic acid 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Cell-Permeable and Plasma-Stable Peptidomimetic Inhibitors of the Postsynaptic Density-95/N-Methyl-d-Aspartate Receptor Interaction

  摘要：

  The protein protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be :replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETA(s)V (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.

  DOI：

  10.1021/jm1013924
• 作为产物：
  描述：

  在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 (2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoic acid
  参考文献：
  名称：

  一种含肽类化合物的冷冻保存液在卵母细胞或胚胎冻存中的应用

  摘要：

  本发明公开了一种肽类化合物和含有该化合物的冷冻保存液。所述肽类化合物由亲冰氨基酸和亲水基团组成，在水溶液中具有良好的抑制冰晶生长和修饰冰晶形貌的能力，且没有热滞后，生物相容性好，是理想的控冰材料。含有上述肽类化合物的冷冻保存液含有上述肽类化合物和多元醇、水溶性糖等组分，用于胚胎或卵母细胞保存可保持良好的存活率，成分简单，性能稳定。

  公开号：

  CN111789099B

文献信息

• Efficient N-Terminal Labeling of Proteins by Use of Sortase
  作者：Daniel J. Williamson、Martin A. Fascione、Michael E. Webb、W. Bruce Turnbull

  DOI：10.1002/anie.201204538

  日期：2012.9.10

  “Sorting out” N‐terminal labeling: The reversibility of transpeptidase reactions makes protein N‐terminal labeling challenging. Depsipeptide substrates for sortase A release alcohol by‐products, which are poor nucleophiles for the reverse reaction, during ligation. Proteins with an unhindered N‐terminal glycine residue can be labeled efficiently with only a minimal excess of the labeling reagent (see scheme)

  “整理” N 端标记：转肽酶反应的可逆性使蛋白质 N 端标记具有挑战性。分选酶 A 的缩肽底物在连接过程中释放醇副产物，这些副产物是逆反应的不良亲核试剂。具有不受阻碍的 N 末端甘氨酸残基的蛋白质只需少量过量的标记试剂即可有效标记（见方案）。
• 一种含肽类化合物的冷冻保存液在卵母细胞或胚胎冻存中的应用
  申请人：北京大学第三医院

  公开号：CN111789099B

  公开（公告）日：2022-09-06

  本发明公开了一种肽类化合物和含有该化合物的冷冻保存液。所述肽类化合物由亲冰氨基酸和亲水基团组成，在水溶液中具有良好的抑制冰晶生长和修饰冰晶形貌的能力，且没有热滞后，生物相容性好，是理想的控冰材料。含有上述肽类化合物的冷冻保存液含有上述肽类化合物和多元醇、水溶性糖等组分，用于胚胎或卵母细胞保存可保持良好的存活率，成分简单，性能稳定。
• TARGETING AMINOACID LIPIDS
  申请人：Merck Patent GmbH

  公开号：EP2825156B1

  公开（公告）日：2017-07-26
• Cell-Permeable and Plasma-Stable Peptidomimetic Inhibitors of the Postsynaptic Density-95/<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Interaction
  作者：Anders Bach、Jonas N. N. Eildal、Nicolai Stuhr-Hansen、Rasmus Deeskamp、Marie Gottschalk、Søren W. Pedersen、Anders S. Kristensen、Kristian Strømgaard

  DOI：10.1021/jm1013924

  日期：2011.3.10

  The protein protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be :replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETA(s)V (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.