(S)-2-{(R)-1-[(S)-2-tert-Butoxycarbonylamino-3-(4-tert-butoxy-phenyl)-propionyl]-6-oxo-1,7-diaza-spiro[4.4]non-7-yl}-3-(4-tert-butoxy-phenyl)-propionic acid | 121773-01-1

• 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)-2-{(R)-1-[(S)-2-tert-Butoxycarbonylamino-3-(4-tert-butoxy-phenyl)-propionyl]-6-oxo-1,7-diaza-spiro[4.4]non-7-yl}-3-(4-tert-butoxy-phenyl)-propionic acid
• CAS: 121773-01-1
• 化学式: C₃₈H₅₃N₃O₈
• 分子量: 679.854
• InChiKey: NADAOJYQMCRRQG-XOYPNWLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.77
• 重原子数：
  49.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  134.71
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  五氟苯酚 、 (S)-2-{(R)-1-[(S)-2-tert-Butoxycarbonylamino-3-(4-tert-butoxy-phenyl)-propionyl]-6-oxo-1,7-diaza-spiro[4.4]non-7-yl}-3-(4-tert-butoxy-phenyl)-propionic acid 在 N,N'-二异丙基碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 以55%的产率得到(2,3,4,5,6-pentafluorophenyl) (2S)-2-[(5R)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoyl]-6-oxo-1,7-diazaspiro[4.4]nonan-7-yl]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoate
  参考文献：
  名称：

  新型肽β-turn模拟物的设计与合成

  摘要：

  描述了新型螺环单元（7）的立体定向合成及其在固相方法中的结构，该结构为免疫显性九肽（1）的构象锁定类似物。

  DOI：

  10.1039/c39880001447
• 作为产物：
  描述：

  benzyl (5R)-7-[(2S)-1-methoxy-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]-1-oxopropan-2-yl]-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-{(R)-1-[(S)-2-tert-Butoxycarbonylamino-3-(4-tert-butoxy-phenyl)-propionyl]-6-oxo-1,7-diaza-spiro[4.4]non-7-yl}-3-(4-tert-butoxy-phenyl)-propionic acid
  参考文献：
  名称：

  新型肽β-turn模拟物的设计与合成

  摘要：

  描述了新型螺环单元（7）的立体定向合成及其在固相方法中的结构，该结构为免疫显性九肽（1）的构象锁定类似物。

  DOI：

  10.1039/c39880001447

文献信息

• Synthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivatives
  作者：Mark G. Hinds、John H. Welsh、David M. Brennand、J. Fisher、Martin J. Glennie、Nigel G. J. Richards、David L. Turner、John A. Robinson

  DOI：10.1021/jm00110a005

  日期：1991.6

  Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.