(D)-isoglutamine methyl ester hydrochloride | 110352-14-2

• 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: (D)-isoglutamine methyl ester hydrochloride
• 英文别名: methyl (4R)-4,5-diamino-5-oxopentanoate;hydrochloride
• CAS: 110352-14-2
• 化学式: C₆H₁₂N₂O₃*ClH
• 分子量: 196.634
• InChiKey: CFJYPWQHBLMCCU-PGMHMLKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.83
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  95.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (D)-isoglutamine methyl ester hydrochloride 在 palladium on activated charcoal N-羟基丁二酰亚胺 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 溶剂黄146 为溶剂， 反应 55.0h， 生成 N-(2-acetamido-2,3-dideoxy-D-glucopyranosid-3-yl)glycyl-D-isoglutamine methyl ester
  参考文献：
  名称：

  Calvo-Mateo, Ana; Heras, Federico G. De las, Liebigs Annalen der Chemie, 1987, p. 1017 - 1020

  摘要：

  DOI：

文献信息

• Synthesis of New Lipophilic Phosphonate and Phosphonamidate Analogues of N-Acetylmuramyl-L-alanyl-D-isoglutamine Related to LK 423
  作者：Stanislav Gobec、Uroš Urleb

  DOI：10.3390/70400394

  日期：——

  A syntheses of three new muramyl dipeptide (MDP) analogues related to LK 423 as potential immunomodulators are presented. The dipeptide part of the lead compound was modified by introducing a phosphonamide isostere instead of the amide bond between Lalanine and D-glutamic acid (or D-isoglutamine), yielding new MDP analogues 5 and 9. Furthermore, the amide bond between L-Ala and D-Glu was replaced by a phosphonate isostere, giving peptidyl phosphonate 14. The scope and limitations of the synthetic strategies employed are discussed.

  本文介绍了三种与LK 423相关的新型肽聚糖二肽（MDP）类似物，作为潜在的免疫调节剂。通过用磷酰胺异构体替代L-丙氨酸和D-谷氨酸（或D-异谷氨酸）之间的酰胺键，修改了主要化合物的二肽部分，得到新的MDP类似物5和9。此外，L-丙氨酸和D-谷氨酸之间的酰胺键被磷酸酯异构体替代，生成了肽磷酸酯14。讨论了所采用合成策略的范围和局限性。
• Membrane Association Dictates Ligand Specificity for the Innate Immune Receptor NOD2
  作者：Amy K. Schaefer、James E. Melnyk、Michael M. Baksh、Klare M. Lazor、M. G. Finn、Catherine Leimkuhler Grimes

  DOI：10.1021/acschembio.7b00469

  日期：2017.8.18

  The human gut must regulate its immune response to resident and pathogenic bacteria, numbering in the trillions. The peptidoglycan component of the bacterial cell wall is a dense and rigid structure that consists of polymeric carbohydrates and highly cross-linked peptides which offers protection from the host and surrounding environment. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a human membrane-associated innate immune receptor found in the gut epithelium and mutated in an estimated 30% of Crohn's disease patients, binds to peptidoglycan fragments and initiates an immune response. Using a combination of chemical synthesis, advanced analytical assays, and protein biochemistry, we tested the binding of a variety,of synthetic peptidoglycan fragments to wild-type (WT)-NOD2. Only when the protein was presented in the native membrane did binding measurements correlate with a NOD2-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) response, supporting the hypothesis that the native-membrane environment confers ligand specificity to the NOD2 receptor for NF-KB signaling. While N-acetyl-muramyl dipeptide (MDP) has been thought to be the minimal peptidoglycan fragment necessary to activate a NOD2-dependent immune response, we found that fragments with and without the dipeptide moiety are capable of binding and activating, a NOD2-dependent NF-KB response, suggesting that the carbohydrate moiety of the peptidoglycan fragments is the minimal functional epitope. This work highlights the necessity of studying NOD2-ligand binding in systems that resemble the receptor's natural environment, as the cellular membrane and/or NOD2 interacting, partners appear to play a crucial role in ligand binding and in triggering an innate immune response.