methyl (1S,2R)-1-[[(2S)-2-[[(2S)-2-formamido-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]-2-phenylcyclopropane-1-carboxylate | 143796-76-3

• 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: methyl (1S,2R)-1-[[(2S)-2-[[(2S)-2-formamido-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]-2-phenylcyclopropane-1-carboxylate
• CAS: 143796-76-3
• 化学式: C₂₃H₃₃N₃O₅S
• 分子量: 463.598
• InChiKey: FIWQTYMXIIZNFR-XQQXVUDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-(2RS)-cyclopropyl-E-phenylalanine 在 茴香硫醚 、 硫酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.75h， 生成 methyl (1S,2R)-1-[[(2S)-2-[[(2S)-2-formamido-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]-2-phenylcyclopropane-1-carboxylate
  参考文献：
  名称：

  A formyl peptide substituted with a conformationally constrained phenylalanine residue evokes a selective immune response in human neutrophils

  摘要：

  Formyl-Met-Leu-Phe-OH (fMLP) binds to formyl peptide receptors, FPR1 and FPR2, and evokes migration and superoxide anion production in human neutrophils. To obtain a more effective and selective ligand, fMLP analogs in which the Phe residue was substituted with four isomers of cyclopropanephenylalanine were synthesized. While Z-isomer peptides induced both migration and superoxide anion production, E-isomer peptides elicited only chemotaxis. Homologous receptor desensitization experiments revealed that E-isomer peptides bound to FPR2. Although a selective agonist of chemotaxis also binds to FPR2 without increasing intracellular calcium concentration, E-isomer peptide elevated the concentration to the same level as fMLP. Understanding of mechanisms responsible for the selectivity of the reported selective agonists and rPhe-substituted analogs should prove useful for revealing the relationship between receptor-ligand interactions and biological responses of human neutrophils. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.046

文献信息

• A formyl peptide substituted with a conformationally constrained phenylalanine residue evokes a selective immune response in human neutrophils
  作者：Ryo Hayashi、Masaya Miyazaki、Satoshi Osada、Hiroshi Kawasaki、Ichiro Fujita、Yuhei Hamasaki、Hiroaki Kodama

  DOI：10.1016/j.bmc.2012.11.046

  日期：2013.2

  Formyl-Met-Leu-Phe-OH (fMLP) binds to formyl peptide receptors, FPR1 and FPR2, and evokes migration and superoxide anion production in human neutrophils. To obtain a more effective and selective ligand, fMLP analogs in which the Phe residue was substituted with four isomers of cyclopropanephenylalanine were synthesized. While Z-isomer peptides induced both migration and superoxide anion production, E-isomer peptides elicited only chemotaxis. Homologous receptor desensitization experiments revealed that E-isomer peptides bound to FPR2. Although a selective agonist of chemotaxis also binds to FPR2 without increasing intracellular calcium concentration, E-isomer peptide elevated the concentration to the same level as fMLP. Understanding of mechanisms responsible for the selectivity of the reported selective agonists and rPhe-substituted analogs should prove useful for revealing the relationship between receptor-ligand interactions and biological responses of human neutrophils. (C) 2012 Elsevier Ltd. All rights reserved.