Ac-Phe-Ala-Leu-Lys(Me3)-Ac5c-ol | 1585186-42-0

• 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: Ac-Phe-Ala-Leu-Lys(Me3)-Ac5c-ol
• 英文别名: [(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-[[1-(hydroxymethyl)cyclopentyl]amino]-6-oxohexyl]-trimethylazanium
• CAS: 1585186-42-0
• 化学式: C₃₅H₅₉N₆O₆
• 分子量: 659.89
• InChiKey: SVEXWFCEEVBBRH-ABYARXGNSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  47
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  166
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Ac-Phe-Ala-Leu-Lys(Me3)-OH 、 1-氨基-1-环戊基甲醇 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Ac-Phe-Ala-Leu-Lys(Me3)-Ac5c-ol
  参考文献：
  名称：

  Chromodomain Antagonists That Target the Polycomb-Group Methyllysine Reader Protein Chromobox Homolog 7 (CBX7)

  摘要：

  We report here a peptide-driven approach to create first inhibitors of the chromobox homolog 7 (CBX7), a methyllysine reader protein. CBX7 uses its chromodomain to bind histone 3, lysine 27 trimethylated (H3K27me3), and this recognition event is implicated in silencing multiple tumor suppressors. Small trimethyllysine containing peptides were used as the basic scaffold from which potent ligands for disruption of CBX7-H3K27me3 complex were developed. Potency of ligands was determined by fluorescence polarization and/or isothermal titration calorimetry. Binding of one ligand was characterized in detail using 2D NMR and X-ray crystallography, revealing a structural motif unique among human CBX proteins. Inhibitors with a similar to 200 nM potency for CBX7 binding and 10-fold/400-fold selectivity over related CBX8/CBX1 proteins were identified. These are the first reported inhibitors of any chromodomain.

  DOI：

  10.1021/jm401487x

文献信息

• Chromodomain Antagonists That Target the Polycomb-Group Methyllysine Reader Protein Chromobox Homolog 7 (CBX7)
  作者：Chakravarthi Simhadri、Kevin D. Daze、Sarah F. Douglas、Taylor T. H. Quon、Amarjot Dev、Michael C. Gignac、Fangni Peng、Markus Heller、Martin J. Boulanger、Jeremy E. Wulff、Fraser Hof

  DOI：10.1021/jm401487x

  日期：2014.4.10

  We report here a peptide-driven approach to create first inhibitors of the chromobox homolog 7 (CBX7), a methyllysine reader protein. CBX7 uses its chromodomain to bind histone 3, lysine 27 trimethylated (H3K27me3), and this recognition event is implicated in silencing multiple tumor suppressors. Small trimethyllysine containing peptides were used as the basic scaffold from which potent ligands for disruption of CBX7-H3K27me3 complex were developed. Potency of ligands was determined by fluorescence polarization and/or isothermal titration calorimetry. Binding of one ligand was characterized in detail using 2D NMR and X-ray crystallography, revealing a structural motif unique among human CBX proteins. Inhibitors with a similar to 200 nM potency for CBX7 binding and 10-fold/400-fold selectivity over related CBX8/CBX1 proteins were identified. These are the first reported inhibitors of any chromodomain.