(1R,2E,5S)-1,5-dicarboxy-5-{[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino}-2-penten-1-aminium 2,2,2-trifluoroacetate

• 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: (1R,2E,5S)-1,5-dicarboxy-5-{[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino}-2-penten-1-aminium 2,2,2-trifluoroacetate
• 英文别名: (E,2R,6S)-2-amino-6-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]hept-3-enedioic acid;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₄H₄₁N₃O₈
• 分子量: 613.629
• InChiKey: ANPVVIQONRJPNV-NEPYBHLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.82
• 重原子数：
  42
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  233
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  (S)-(-)-2-氨基-4-戊烯酸 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 三氟化硼乙醚 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 环己烷 、 水 为溶剂， 反应 3.5h， 生成 (1R,2E,5S)-1,5-dicarboxy-5-{[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino}-2-penten-1-aminium 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Synthesis of conformationally constrained γ-d-glutamyl-meso-diaminopimelic acid derivatives as ligands of nucleotide-binding oligomerization domain protein 1 (Nod1)

  摘要：

  Nod1, an important member of the pattern recognition receptor family, remains a virtually unexploited target. Harnessing its innate immune stimulatory properties still remains an unfulfilled goal of medicinal chemistry. Nucleotide-binding oligomerization domain protein 1 (Nod1) agonists have been shown to boost the inflammatory responses against pathogenic microbes and could thus constitute a new class of broad spectrum antimicrobial agents. To gain additional insight into the structure/activity relationships of Nod1 agonistic compounds, a series of novel, conformationally constrained gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) analogs have been designed and synthesized. Ramos-Blue cells expressing Nod1 were used to screen and validate our compounds for their Nod1-agonist activity. Their immunomodulatory properties were subsequently determined in vitro, by evaluating their capacity to induce proinflammatory cytokine and chemokine production from human peripheral blood mononuclear cells (PBMC), by themselves and in synergy with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand. The synthesized iE-DAP analogs were shown to possess immuno-enhancing properties as a result of their potent and specific Nod1-agonistic effect. The activity of the compound exhibiting the greatest capacity to induce pro-inflammatory cytokine release from PBMC surpassed that of lauroyl-gamma-D-glutamyl-mesodiaminopimelic acid (C12-iE-DAP). (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.022

文献信息

• Synthesis of conformationally constrained γ-d-glutamyl-meso-diaminopimelic acid derivatives as ligands of nucleotide-binding oligomerization domain protein 1 (Nod1)
  作者：Žiga Jakopin、Martina Gobec、Jaka Kodela、Toni Hazdovac、Irena Mlinarič-Raščan、Marija Sollner Dolenc

  DOI：10.1016/j.ejmech.2013.08.022

  日期：2013.11

  Nod1, an important member of the pattern recognition receptor family, remains a virtually unexploited target. Harnessing its innate immune stimulatory properties still remains an unfulfilled goal of medicinal chemistry. Nucleotide-binding oligomerization domain protein 1 (Nod1) agonists have been shown to boost the inflammatory responses against pathogenic microbes and could thus constitute a new class of broad spectrum antimicrobial agents. To gain additional insight into the structure/activity relationships of Nod1 agonistic compounds, a series of novel, conformationally constrained gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) analogs have been designed and synthesized. Ramos-Blue cells expressing Nod1 were used to screen and validate our compounds for their Nod1-agonist activity. Their immunomodulatory properties were subsequently determined in vitro, by evaluating their capacity to induce proinflammatory cytokine and chemokine production from human peripheral blood mononuclear cells (PBMC), by themselves and in synergy with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand. The synthesized iE-DAP analogs were shown to possess immuno-enhancing properties as a result of their potent and specific Nod1-agonistic effect. The activity of the compound exhibiting the greatest capacity to induce pro-inflammatory cytokine release from PBMC surpassed that of lauroyl-gamma-D-glutamyl-mesodiaminopimelic acid (C12-iE-DAP). (C) 2013 Elsevier Masson SAS. All rights reserved.