2-(2-(2-acetamido-4-methylpentanamido)-3-(1-(3-(2-chloroacetamido)propyl)-1H-1,2,3-triazol-4-yl)propanamido)-6-aminohexanamide | 1442419-36-4

• 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: 2-(2-(2-acetamido-4-methylpentanamido)-3-(1-(3-(2-chloroacetamido)propyl)-1H-1,2,3-triazol-4-yl)propanamido)-6-aminohexanamide
• CAS: 1442419-36-4
• 化学式: C₂₄H₄₂ClN₉O₅
• 分子量: 572.108
• InChiKey: AHHMZFDJRRUDCU-UFYCRDLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  39.0
• 可旋转键数：
  19.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  216.22
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-(2-(2-acetamido-4-methylpentanamido)-3-(1-(3-(2-chloroacetamido)propyl)-1H-1,2,3-triazol-4-yl)propanamido)-6-aminohexanamide 、 Cy5-NHS 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以70%的产率得到
  参考文献：
  名称：

  Coupling Protein Engineering with Probe Design To Inhibit and Image Matrix Metalloproteinases with Controlled Specificity

  摘要：

  Matrix metalloproteinases (MMPs) are zinc endopeptidases that play roles in numerous pathophysiological processes and therefore are promising drug targets. However, the large size of this family and a lack of highly selective compounds that can be used for imaging or inhibition of specific MMPs members has limited efforts to better define their biological function. Here we describe a protein engineering strategy coupled with small-molecule probe design to selectively target individual members of the MMP family. Specifically, we introduce a cysteine residue near the active-site of a selected protease that does not alter its overall activity or function but allows direct covalent modification by a small-molecule probe containing a reactive electrophile. This specific engineered interaction between the probe and the target protease provides a means to both image and inhibit the modified protease with absolute specificity. Here we demonstrate the feasibility of the approach for two distinct MMP proteases, MMP-12 and MT1-MMP (or MMP-14).

  DOI：

  10.1021/ja403523p
• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 N-(3-azidopropyl)-2-chloroacetamide 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 Fmoc-L-炔丙基甘氨酸 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以50%的产率得到2-(2-(2-acetamido-4-methylpentanamido)-3-(1-(3-(2-chloroacetamido)propyl)-1H-1,2,3-triazol-4-yl)propanamido)-6-aminohexanamide
  参考文献：
  名称：

  Coupling Protein Engineering with Probe Design To Inhibit and Image Matrix Metalloproteinases with Controlled Specificity

  摘要：

  Matrix metalloproteinases (MMPs) are zinc endopeptidases that play roles in numerous pathophysiological processes and therefore are promising drug targets. However, the large size of this family and a lack of highly selective compounds that can be used for imaging or inhibition of specific MMPs members has limited efforts to better define their biological function. Here we describe a protein engineering strategy coupled with small-molecule probe design to selectively target individual members of the MMP family. Specifically, we introduce a cysteine residue near the active-site of a selected protease that does not alter its overall activity or function but allows direct covalent modification by a small-molecule probe containing a reactive electrophile. This specific engineered interaction between the probe and the target protease provides a means to both image and inhibit the modified protease with absolute specificity. Here we demonstrate the feasibility of the approach for two distinct MMP proteases, MMP-12 and MT1-MMP (or MMP-14).

  DOI：

  10.1021/ja403523p