N,N'-(hexa-2,4-diyne-1,6-diyl)bis{(2'S)-2'-tert-butoxycarbonylamino-4'-[5''-deoxy-5''-(methylamino)-2'',3''-O-(1'''-methylethylidene)adenosyl]butanamide} | 1355023-94-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N,N'-(hexa-2,4-diyne-1,6-diyl)bis{(2'S)-2'-tert-butoxycarbonylamino-4'-[5''-deoxy-5''-(methylamino)-2'',3''-O-(1'''-methylethylidene)adenosyl]butanamide}
• CAS: 1355023-94-7
• 化学式: C₅₂H₇₄N₁₆O₁₂
• 分子量: 1115.26
• InChiKey: BXUBUZCMXWYWGZ-CMQZGFMDSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  80.0
• 可旋转键数：
  18.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  335.96
• 氢给体数：
  6.0
• 氢受体数：
  24.0

反应信息

• 作为反应物：
  描述：

  N,N'-(hexa-2,4-diyne-1,6-diyl)bis{(2'S)-2'-tert-butoxycarbonylamino-4'-[5''-deoxy-5''-(methylamino)-2'',3''-O-(1'''-methylethylidene)adenosyl]butanamide} 在 盐酸 、 水 作用下， 反应 0.25h， 以84%的产率得到N,N'-(hexa-2,4-diyne-1,6-diyl)bis{(2'S)-2'-amino-4'-[5''-deoxy-5''-(methylamino)-adenosyl]butanamide}
  参考文献：
  名称：

  Design, synthesis and in vitro evaluation of novel bivalent S-adenosylmethionine analogues

  摘要：

  In optimal cases, bivalent ligands can bind with exceptionally high affinity to their protein targets. However, designing optimised linkers, that orient the two binding groups perfectly, is challenging, and yet crucial in both fragment-based ligand design and in the discovery of bisubstrate enzyme inhibitors. To further our understanding of linker design, a series of novel bivalent S-adenosylmethionine (SAM) analogues were designed with the aim of interacting with the MetJ dimer in a bivalent sense (1:1 ligand/MetJ dimer). A range of ligands was synthesised and analyzed for ability to promote binding of the Escherichia coli methionine repressor, MetJ, to its operator DNA. Binding of bivalent SAM analogues to the MetJ homodimer in the presence of operator DNA was evaluated by fluorescence anisotropy and the effect of linker length and structure was investigated. The most effective bivalent ligand identified had a flexible linker, and promoted the DNA-protein interaction at 21-times lower concentration than the corresponding monovalent control compound. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.017
• 作为产物：
  描述：

  (S)-4-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)-2-((tert-butoxycarbonyl)amino)butanoic acid 在 吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 copper(l) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 N,N'-(hexa-2,4-diyne-1,6-diyl)bis{(2'S)-2'-tert-butoxycarbonylamino-4'-[5''-deoxy-5''-(methylamino)-2'',3''-O-(1'''-methylethylidene)adenosyl]butanamide}
  参考文献：
  名称：

  Design, synthesis and in vitro evaluation of novel bivalent S-adenosylmethionine analogues

  摘要：

  In optimal cases, bivalent ligands can bind with exceptionally high affinity to their protein targets. However, designing optimised linkers, that orient the two binding groups perfectly, is challenging, and yet crucial in both fragment-based ligand design and in the discovery of bisubstrate enzyme inhibitors. To further our understanding of linker design, a series of novel bivalent S-adenosylmethionine (SAM) analogues were designed with the aim of interacting with the MetJ dimer in a bivalent sense (1:1 ligand/MetJ dimer). A range of ligands was synthesised and analyzed for ability to promote binding of the Escherichia coli methionine repressor, MetJ, to its operator DNA. Binding of bivalent SAM analogues to the MetJ homodimer in the presence of operator DNA was evaluated by fluorescence anisotropy and the effect of linker length and structure was investigated. The most effective bivalent ligand identified had a flexible linker, and promoted the DNA-protein interaction at 21-times lower concentration than the corresponding monovalent control compound. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.017