(S)-N-((S)-1-amino-1-oxo-3-phenylpropan-2-yl)-2-(2-mercaptoacetamido)-4-(methylthio)butanamide | 1197393-04-6

• 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: (S)-N-((S)-1-amino-1-oxo-3-phenylpropan-2-yl)-2-(2-mercaptoacetamido)-4-(methylthio)butanamide
• 英文别名: (2S)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-methylsulfanyl-2-[(2-sulfanylacetyl)amino]butanamide
• CAS: 1197393-04-6
• 化学式: C₁₆H₂₃N₃O₃S₂
• 分子量: 369.509
• InChiKey: BQPLGKSFJPHSSG-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(三苯甲游基硫代)乙酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-蛋氨酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-N-((S)-1-amino-1-oxo-3-phenylpropan-2-yl)-2-(2-mercaptoacetamido)-4-(methylthio)butanamide
  参考文献：
  名称：

  Inhibitor profiling of the Pseudomonas aeruginosa virulence factor LasB using N-alpha mercaptoamide template-based inhibitors

  摘要：

  We report on the synthesis and biological evaluation of a focussed library of N-alpha mercaptoamide containing dipeptides as inhibitors of the zinc metallopeptidase Pseudomonas aeruginosa elastase (LasB, EC 3.4.24.26). The aim of the study was to derive an inhibitor pro. le for LasB with regard to mapping the S-1' binding site of the enzyme. Consequently, a focussed library of 160 members has been synthesised, using standard Fmoc-solid phase methods (on a Rink-amide resin), in which a subset of amino acids including examples of those with basic (Lys, Arg), aromatic (Phe, Trp), large aliphatic (Val, Leu) and acidic (Asp, Glu) side-chains populated the P-2' position of the inhibitor sequence and all 20 natural amino acids were incorporated, in turn, at the P-1' position. The study has revealed a preference for aromatic and/or large aliphatic amino acids at P-1' and a distinct bias against acidic residues at P-2'. Ten inhibitor sequences were discovered that exhibited sub to low micromolar K-i values. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.099

文献信息

• Inhibitor profiling of the Pseudomonas aeruginosa virulence factor LasB using N-alpha mercaptoamide template-based inhibitors
  作者：George R. Cathcart、Brendan F. Gilmore、Brett Greer、Pat Harriott、Brian Walker

  DOI：10.1016/j.bmcl.2009.08.099

  日期：2009.11

  We report on the synthesis and biological evaluation of a focussed library of N-alpha mercaptoamide containing dipeptides as inhibitors of the zinc metallopeptidase Pseudomonas aeruginosa elastase (LasB, EC 3.4.24.26). The aim of the study was to derive an inhibitor pro. le for LasB with regard to mapping the S-1' binding site of the enzyme. Consequently, a focussed library of 160 members has been synthesised, using standard Fmoc-solid phase methods (on a Rink-amide resin), in which a subset of amino acids including examples of those with basic (Lys, Arg), aromatic (Phe, Trp), large aliphatic (Val, Leu) and acidic (Asp, Glu) side-chains populated the P-2' position of the inhibitor sequence and all 20 natural amino acids were incorporated, in turn, at the P-1' position. The study has revealed a preference for aromatic and/or large aliphatic amino acids at P-1' and a distinct bias against acidic residues at P-2'. Ten inhibitor sequences were discovered that exhibited sub to low micromolar K-i values. (C) 2009 Elsevier Ltd. All rights reserved.