N-acetyl-L-isoleucyl-L-leucine | 92208-91-8

• 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: N-acetyl-L-isoleucyl-L-leucine
• 英文别名: Ac-L-Ile-L-Leu；(2S)-2-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-4-methylpentanoic acid
• CAS: 92208-91-8
• 化学式: C₁₄H₂₆N₂O₄
• 分子量: 286.371
• InChiKey: XAYGFAMQVLYZAB-DLOVCJGASA-N

物化性质

• 沸点：
  540.4±35.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.15
• 重原子数：
  20.0
• 可旋转键数：
  8.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  95.5
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-acetyl-L-isoleucyl-L-leucine 在 2,4,6-三甲基吡啶 、 碘代三甲硅烷 、 茴香硫醚 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 N-(N-acetyl-L-isoleucyl-L-leucyl)-1-amino-2-(4-hydoxyphenyl)ethylphosphonic acid
  参考文献：
  名称：

  Interkingdom Pharmacology of Angiotensin-I Converting Enzyme Inhibitor Phosphonates Produced by Actinomycetes

  摘要：

  The K-26 family of bacterial secondary metabolites are N-modified tripeptides terminated by an unusual phosphonate analog of tyrosine. These natural products, produced via three different actinomycetales, are potent inhibitors of human angiotensin-I converting enzyme (ACE). Herein we investigate the interkingdom pharmacology of the K-26 family by synthesizing these metabolites and assessing their potency as inhibitors of both the N-terminal and C-terminal domains of human ACE. In most cases, selectivity for the C-terminal domain of ACE is displayed. Co-crystallization of K-26 in both domains of human ACE reveals the structural basis of the potent inhibition and has shown an unusual binding motif that may guide future design of domain-selective inhibitors. Finally, the activity of K-26 is assayed against a cohort of microbially produced ACE relatives. In contrast to the synthetic ACE inhibitor captopril, which demonstrates broad interkingdom inhibition of ACE-like enzymes, K-26 selectively targets the eukaryotic family.

  DOI：

  10.1021/ml4004588
• 作为产物：
  描述：

  L-亮氨酸甲酯盐酸盐 在 2,4,6-三甲基吡啶 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 N-acetyl-L-isoleucyl-L-leucine
  参考文献：
  名称：

  Interkingdom Pharmacology of Angiotensin-I Converting Enzyme Inhibitor Phosphonates Produced by Actinomycetes

  摘要：

  The K-26 family of bacterial secondary metabolites are N-modified tripeptides terminated by an unusual phosphonate analog of tyrosine. These natural products, produced via three different actinomycetales, are potent inhibitors of human angiotensin-I converting enzyme (ACE). Herein we investigate the interkingdom pharmacology of the K-26 family by synthesizing these metabolites and assessing their potency as inhibitors of both the N-terminal and C-terminal domains of human ACE. In most cases, selectivity for the C-terminal domain of ACE is displayed. Co-crystallization of K-26 in both domains of human ACE reveals the structural basis of the potent inhibition and has shown an unusual binding motif that may guide future design of domain-selective inhibitors. Finally, the activity of K-26 is assayed against a cohort of microbially produced ACE relatives. In contrast to the synthetic ACE inhibitor captopril, which demonstrates broad interkingdom inhibition of ACE-like enzymes, K-26 selectively targets the eukaryotic family.

  DOI：

  10.1021/ml4004588

文献信息

• HETEROLOGOUS PRODUCTION OF LEUPEPTIN PROTEASE INHIBITORS AND ANALOGS THEREOF
  申请人：YALE UNIVERSITY

  公开号：US20220002354A1

  公开（公告）日：2022-01-06

  The present disclosure includes a construct comprising a leupeptin biosynthesis operon, the operon comprising leupA, leupB, leupC, and leupD genes operably linked to a promoter. Also included are cells comprising the construct, and methods for production of leupeptin peptide.

  本公开涵盖了一个包含琥珀胺生物合成操纵子的构建物，该操纵子包括与启动子可操作连接的leupA、leupB、leupC和leupD基因。还包括包含该构建物的细胞，以及琥珀胺肽的生产方法。