N6-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-赖氨酸 | 214852-52-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N6-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-赖氨酸
• 英文名称: Fmoc-Har(Pmc)-OH
• 英文别名: Fmoc-Homoarg(Pmc)-OH；(2S)-6-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid
• CAS: 214852-52-5
• 化学式: C₃₆H₄₄N₄O₇S
• 分子量: 676.834
• InChiKey: ZZSYLAIWMWFQRW-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N6-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-N2-[(9H-芴-9-基甲氧基)羰基]-L-赖氨酸 、 芴甲氧羰酰基高苯丙氨酸 、 Fmoc-L-正缬氨酸 、 N-Fmoc-N'-Boc-L-2,3-二氨基丙酸 、 Fmoc-3-(2-萘基)-L-丙氨酸 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 乙酸酐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 Hph-Nva-Dap-Har-Nal-Nva
  参考文献：
  名称：

  Proteochemometrics mapping of the interaction space for retroviral proteases and their substrates

  摘要：

  Understanding the complex interactions of retroviral proteases with their ligands is an important scientific challenge in efforts to achieve control of retroviral infections. Development of drug resistance because of high mutation rates and extensive polymorphisms causes major problems in treating the deadly diseases these viruses cause, and prompts efforts to identify new strategies. Here we report a comprehensive analysis of the interaction of 63 retroviral proteases from nine different viral species with their substrates and inhibitors based on publicly available data from the past 17 years of retroviral research. By correlating physico-chemical descriptions of retroviral proteases and substrates to their biological activities we constructed a highly statistically valid 'proteochemometric' model for the interactome of retroviral proteases. Analysis of the model indicated amino acid positions in retroviral proteases with the highest influence on ligand activity and revealed general physicochemical properties essential for tight binding of substrates across multiple retroviral proteases. Hexapeptide inhibitors developed based on the discovered general properties effectively inhibited HIV-1 proteases in vitro, and some exhibited uniformly high inhibitory activity against all HIV-1 proteases mutants evaluated. A generalized proteochemometric model for retroviral proteases interactome has been created and analysed in this study. Our results demonstrate the feasibility of using the developed general strategy in the design of inhibitory peptides that can potentially serve as templates for drug resistance-improved HIV retardants. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.045

文献信息

• Proteochemometrics mapping of the interaction space for retroviral proteases and their substrates
  作者：Aleksejs Kontijevskis、Ramona Petrovska、Sviatlana Yahorava、Jan Komorowski、Jarl E.S. Wikberg

  DOI：10.1016/j.bmc.2009.05.045

  日期：2009.7

  Understanding the complex interactions of retroviral proteases with their ligands is an important scientific challenge in efforts to achieve control of retroviral infections. Development of drug resistance because of high mutation rates and extensive polymorphisms causes major problems in treating the deadly diseases these viruses cause, and prompts efforts to identify new strategies. Here we report a comprehensive analysis of the interaction of 63 retroviral proteases from nine different viral species with their substrates and inhibitors based on publicly available data from the past 17 years of retroviral research. By correlating physico-chemical descriptions of retroviral proteases and substrates to their biological activities we constructed a highly statistically valid 'proteochemometric' model for the interactome of retroviral proteases. Analysis of the model indicated amino acid positions in retroviral proteases with the highest influence on ligand activity and revealed general physicochemical properties essential for tight binding of substrates across multiple retroviral proteases. Hexapeptide inhibitors developed based on the discovered general properties effectively inhibited HIV-1 proteases in vitro, and some exhibited uniformly high inhibitory activity against all HIV-1 proteases mutants evaluated. A generalized proteochemometric model for retroviral proteases interactome has been created and analysed in this study. Our results demonstrate the feasibility of using the developed general strategy in the design of inhibitory peptides that can potentially serve as templates for drug resistance-improved HIV retardants. (C) 2009 Elsevier Ltd. All rights reserved.