bz-Arg(NH₂)-Ala-Sta-NH-indane*TFA

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: bz-Arg(NH₂)-Ala-Sta-NH-indane*TFA
• 英文别名: benzyl N-[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1-[[(3S,4S)-1-(2,3-dihydro-1H-inden-2-ylamino)-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]carbamate;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₃₄H₄₉N₇O₆
• 分子量: 765.83
• InChiKey: GLHNCRVLMHIZMS-OSVSPSBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.04
• 重原子数：
  54
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  248
• 氢给体数：
  8
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-(叔丁氧羰基)抑胃酶氨酸 在 盐酸 、 水 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 bz-Arg(NH₂)-Ala-Sta-NH-indane*TFA
  参考文献：
  名称：

  Transition State Mimetics of the Plasmodium Export Element Are Potent Inhibitors of Plasmepsin V from P. falciparum and P. vivax

  摘要：

  Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; RxL down arrow xE/Q/D) in the parasite's endoplasmic reticulum. Here, we generated transition state mimetics of the native PEXEL substrate that potently inhibit PMV isolated from Plasmodium falciparum and Plasmodium vivax. Through optimization, we identified that the activity of the mimetics was completely dependent on the presence of P-1 Leu and P-3 Arg. Treatment of P. falciparum-infected erythrocytes with a set of optimized mimetics impaired PEXEL processing and killed the parasites. The striking effect of the compounds provides a clearer understanding of the accessibility of the PMV active site and reaffirms the enzyme as an attractive target for the design of future antimalarials.

  DOI：

  10.1021/jm500797g