N-­Fmoc-­(2S)-2-­amino-­4-­oxo-­4-­((8-­phenyloctyl)amino)butanoic acid | 1415221-85-0

• 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: N-­Fmoc-­(2S)-2-­amino-­4-­oxo-­4-­((8-­phenyloctyl)amino)butanoic acid
• 英文别名: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-4-(8-phenyloctylamino)butanoic acid
• CAS: 1415221-85-0
• 化学式: C₃₃H₃₈N₂O₅
• 分子量: 542.675
• InChiKey: NRLFZEMKOGYWGJ-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-苯基-1-辛醇 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 magnesium 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-­Fmoc-­(2S)-2-­amino-­4-­oxo-­4-­((8-­phenyloctyl)amino)butanoic acid
  参考文献：
  名称：

  Non-proteinogenic amino acids in the pThr-2 position of a pentamer peptide that confer high binding affinity for the polo box domain (PBD) of polo-like kinase 1 (Plk1)

  摘要：

  We report herein that incorporating long-chain alkylphenyl-containing non-proteinogenic amino acids in place of His at the pT-2 position of the parent polo-like kinase 1 (Plk1) polo box domain (PBD)-binding pentapeptide, PLHSpT (1a) increases affinity. For certain analogs, approximately two orders-of-magnitude improvement in affinity was observed. Although, none of the new analogs was as potent as our previously described peptide 1b, in which the pT-2 histidine imidazole ring is alkylated at its pi nitrogen (N3), our current finding that the isomeric His(N1)-analog (1c) binds with approximately 50-fold less affinity than 1b, indicates the positional importance of attachment to the His imidazole ring. Our demonstration that a range of modified residues at the pT-2 position can enhance binding affinity, should facilitate the development of minimally-sized Plk1 PBD-binding antagonists. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.10.093

文献信息

• Non-proteinogenic amino acids in the pThr-2 position of a pentamer peptide that confer high binding affinity for the polo box domain (PBD) of polo-like kinase 1 (Plk1)
  作者：Wen-Jian Qian、Jung-Eun Park、Kyung S. Lee、Terrence R. Burke

  DOI：10.1016/j.bmcl.2012.10.093

  日期：2012.12

  We report herein that incorporating long-chain alkylphenyl-containing non-proteinogenic amino acids in place of His at the pT-2 position of the parent polo-like kinase 1 (Plk1) polo box domain (PBD)-binding pentapeptide, PLHSpT (1a) increases affinity. For certain analogs, approximately two orders-of-magnitude improvement in affinity was observed. Although, none of the new analogs was as potent as our previously described peptide 1b, in which the pT-2 histidine imidazole ring is alkylated at its pi nitrogen (N3), our current finding that the isomeric His(N1)-analog (1c) binds with approximately 50-fold less affinity than 1b, indicates the positional importance of attachment to the His imidazole ring. Our demonstration that a range of modified residues at the pT-2 position can enhance binding affinity, should facilitate the development of minimally-sized Plk1 PBD-binding antagonists. Published by Elsevier Ltd.