diethyl (2R)-2-[((2S)-2-{[5-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)-pentanoyl]amino}propanoyl)amino]pentanedioate | 1386397-85-8

• 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: diethyl (2R)-2-[((2S)-2-{[5-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)-pentanoyl]amino}propanoyl)amino]pentanedioate
• 英文别名: diethyl (2R)-2-[[(2S)-2-[5-(1,1,3-trioxo-1,2-benzothiazol-2-yl)pentanoylamino]propanoyl]amino]pentanedioate
• CAS: 1386397-85-8
• 化学式: C₂₄H₃₃N₃O₉S
• 分子量: 539.607
• InChiKey: MMDGFXKXRWFQSY-FUHWJXTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  174
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  diethyl L-alanyl-D-glutamate trifluoroacetate 、 5-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)pentanoic acid 在 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 以74%的产率得到diethyl (2R)-2-[((2S)-2-{[5-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)-pentanoyl]amino}propanoyl)amino]pentanedioate
  参考文献：
  名称：

  Immunomodulatory Properties of Novel Nucleotide Oligomerization Domain 2 (Nod2) Agonistic Desmuramyldipeptides

  摘要：

  There is a pressing need for the development of novel adjuvants for human use. The minimal bioactive structure of bacterial peptidoglycan (PGN), muramyldipeptide (MDP), and its derivative murabutide (MB) have long been known for their adjuvant activities. For this reason, a series of novel desmuramyldipepticles have been designed and synthesized as part of our search for therapeutically useful MDP analogues. Since nucleotide oligomerization domain 2 (Nod2) is a putative receptor for MDP, we used engineered HEK293 cells overexpressing Nod2 to screen and validate our compounds for their Nod2-agonist activity. Their immunomodulatory properties were subsequently assessed in vitro by evaluating their effect on proinflammatory cytolcine production of phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells (PBMCs). Herein, we present novel desmuramyldipeptides, the most active of them possessing immunoenhancing properties as a result of their potent Nod2-agonistic effect.

  DOI：

  10.1021/jm300503b

文献信息

• Immunomodulatory Properties of Novel Nucleotide Oligomerization Domain 2 (Nod2) Agonistic Desmuramyldipeptides
  作者：Žiga Jakopin、Martina Gobec、Irena Mlinarič-Raščan、Marija Sollner Dolenc

  DOI：10.1021/jm300503b

  日期：2012.7.26

  There is a pressing need for the development of novel adjuvants for human use. The minimal bioactive structure of bacterial peptidoglycan (PGN), muramyldipeptide (MDP), and its derivative murabutide (MB) have long been known for their adjuvant activities. For this reason, a series of novel desmuramyldipepticles have been designed and synthesized as part of our search for therapeutically useful MDP analogues. Since nucleotide oligomerization domain 2 (Nod2) is a putative receptor for MDP, we used engineered HEK293 cells overexpressing Nod2 to screen and validate our compounds for their Nod2-agonist activity. Their immunomodulatory properties were subsequently assessed in vitro by evaluating their effect on proinflammatory cytolcine production of phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells (PBMCs). Herein, we present novel desmuramyldipeptides, the most active of them possessing immunoenhancing properties as a result of their potent Nod2-agonistic effect.