N-(N-acetyl-L-isoleucyl-L-glutamyl)-1-amino-2-(4-hydroxyphenyl)phosphonic acid | 1557193-46-0

• 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-(N-acetyl-L-isoleucyl-L-glutamyl)-1-amino-2-(4-hydroxyphenyl)phosphonic acid
• 英文别名: (4S)-4-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-5-[[(1R)-2-(4-hydroxyphenyl)-1-phosphonoethyl]amino]-5-oxopentanoic acid
• CAS: 1557193-46-0
• 化学式: C₂₁H₃₂N₃O₉P
• 分子量: 501.474
• InChiKey: JLRSTRPIBMWOKM-CTSOBWNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  202
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-乙酰-L-异亮氨酸 在 2,4,6-三甲基吡啶 、 碘代三甲硅烷 、 三(2-氨基乙基)胺 、 茴香硫醚 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 N-(N-acetyl-L-isoleucyl-L-glutamyl)-1-amino-2-(4-hydroxyphenyl)phosphonic 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

文献信息

• Interkingdom Pharmacology of Angiotensin-I Converting Enzyme Inhibitor Phosphonates Produced by Actinomycetes
  作者：Glenna J. Kramer、Akif Mohd、Sylva L. U. Schwager、Geoffrey Masuyer、K. Ravi Acharya、Edward D. Sturrock、Brian O. Bachmann

  DOI：10.1021/ml4004588

  日期：2014.4.10

  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.