Z-Phe-Arg-methyl (bis-2,6-trifluoromethyl)benzoate | 1252585-66-2

• 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: Z-Phe-Arg-methyl (bis-2,6-trifluoromethyl)benzoate
• 英文别名: [(3S)-6-(diaminomethylideneamino)-2-oxo-3-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]hexyl] 2,6-bis(trifluoromethyl)benzoate
• CAS: 1252585-66-2
• 化学式: C₃₃H₃₃F₆N₅O₆
• 分子量: 709.645
• InChiKey: POBZNINTAIXWMQ-DQEYMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  Z-Phe-Arg(Pbf)-methyl (bis-2,6-trifluoromethyl)benzoate 在 水 、 三氟乙酸 作用下， 反应 4.0h， 生成 Z-Phe-Arg-methyl (bis-2,6-trifluoromethyl)benzoate
  参考文献：
  名称：

  Modulation of the inhibitor properties of dipeptidyl (acyloxy)methyl ketones toward the CaaX proteases

  摘要：

  Dipeptidyl (acyloxy) methyl ketones (AOMKs) have been identified as mechanism-based inhibitors of certain cysteine proteases. These compounds are also inhibitors of the integral membrane proteins Rce1p and Ste24p, which are proteases that independently mediate a cleavage step associated with the maturation of certain isoprenylated proteins. The enzymatic mechanism of Rce1p is ill-defined, whereas Ste24p is a zinc metalloprotease. Rce1p is required for the proper processing of the oncoprotein Ras and is viewed as a potential target for cancer therapy. In this study, we synthesized a small library of dipeptidyl AOMKs to investigate the structural elements that contribute to the inhibitor properties of this class of molecules toward Rce1p and Ste24p. The compounds were evaluated using a fluorescence-based in vitro proteolysis assay. The most potent dipeptidyl AOMKs contained an arginine residue and the identity of the benzoate group strongly influenced potency. A 'warhead' free AOMK inhibited Rce1p and Ste24p. The data suggest that the dipeptidyl AOMKs are not mechanism-based inhibitors of Rce1p and Ste24p and corroborate the hypothesis that Rce1p is not a cysteine protease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.041

文献信息

• Modulation of the inhibitor properties of dipeptidyl (acyloxy)methyl ketones toward the CaaX proteases
  作者：Anne-Marie R. Dechert、James P. MacNamara、Sarah R. Breevoort、Emily R. Hildebrandt、Ned W. Hembree、Adam C. Rea、Duncan E. McLain、Stephen B. Porter、Walter K. Schmidt、Timothy M. Dore

  DOI：10.1016/j.bmc.2010.07.041

  日期：2010.9

  Dipeptidyl (acyloxy) methyl ketones (AOMKs) have been identified as mechanism-based inhibitors of certain cysteine proteases. These compounds are also inhibitors of the integral membrane proteins Rce1p and Ste24p, which are proteases that independently mediate a cleavage step associated with the maturation of certain isoprenylated proteins. The enzymatic mechanism of Rce1p is ill-defined, whereas Ste24p is a zinc metalloprotease. Rce1p is required for the proper processing of the oncoprotein Ras and is viewed as a potential target for cancer therapy. In this study, we synthesized a small library of dipeptidyl AOMKs to investigate the structural elements that contribute to the inhibitor properties of this class of molecules toward Rce1p and Ste24p. The compounds were evaluated using a fluorescence-based in vitro proteolysis assay. The most potent dipeptidyl AOMKs contained an arginine residue and the identity of the benzoate group strongly influenced potency. A 'warhead' free AOMK inhibited Rce1p and Ste24p. The data suggest that the dipeptidyl AOMKs are not mechanism-based inhibitors of Rce1p and Ste24p and corroborate the hypothesis that Rce1p is not a cysteine protease. (C) 2010 Elsevier Ltd. All rights reserved.