PCU-lactam-NH-EAIS | 1309041-93-7

• 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: PCU-lactam-NH-EAIS
• 英文别名: pentacycloundecane-lactam-NH-EAIS；PCU-EAIS；(4S)-4-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-[(1-hydroxy-12-oxo-11-azahexacyclo[5.5.1.02,6.03,10.04,8.09,13]tridecan-10-yl)amino]-5-oxopentanoic acid
• CAS: 1309041-93-7
• 化学式: C₂₉H₄₂N₆O₉
• 分子量: 618.687
• InChiKey: OSKMOKTVGGXEKD-JETBFYLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.5
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  249
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  Glu-Ala-Ile-Ser 、 11-amino-8-hydroxy-pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>undecane-8,11-lactam 在 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 PCU-lactam-NH-EAIS
  参考文献：
  名称：

  Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors: A hybrid 2D NMR and docking/QM/MM/MD approach

  摘要：

  Pentacycloundecane (PCU) lactam-peptide based HIV protease inhibitors were synthesized and nanomolar activity against the resistance-prone wild type C-South African HIV protease is reported. NMR investigations indicated that the activity is related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. EASY-ROESY NMR experiments gave information about the 3D structure of the cage peptides and 3D solution structure could be linked to the experimental IC(50) activity profile of the considered inhibitors. QM/MM/MD simulations of the inhibitors in solution confirmed the NMR observed conformations. Docking experiments and QM/MM/MD simulations of the inhibitor-HIV PR complexes were also performed. These computational results complimented the experimental inhibition activities and enabled us to report a unique binding mode for PCU-based inhibitors at the active site of HIV-protease enzyme. A conserved hydrogen bonding pattern between the norstatine type functional group of the PCU hydroxylactam and active site residues, ASP25/ASP25', was observed in all active compounds. The biological significance and possible mode of inhibition by PCU-based HIV PR inhibitors discussed herein provide us with a deeper understanding of the mode of action of these novel inhibitors. The PCU-peptides are between 6000 and 8500 time less toxic to human MT-4 cells than Lopinavir. This potentially creates new application avenues for these putative inhibitors to be investigated against a vast number of other disease-related proteases. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.071