{2-[6-(2-methoxy-ethoxymethoxy)-benzothiazol-2-yl]-thiazole-4-carbonyl}-sulfamic acid 6-(6-amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester | 865861-15-0

• 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: {2-[6-(2-methoxy-ethoxymethoxy)-benzothiazol-2-yl]-thiazole-4-carbonyl}-sulfamic acid 6-(6-amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester
• CAS: 865861-15-0
• 化学式: C₂₈H₃₀N₈O₁₀S₃
• 分子量: 734.792
• InChiKey: FCVDBWFBHUEZMC-VKUWRZNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  49.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  223.25
• 氢给体数：
  2.0
• 氢受体数：
  19.0

反应信息

• 作为反应物：
  描述：

  {2-[6-(2-methoxy-ethoxymethoxy)-benzothiazol-2-yl]-thiazole-4-carbonyl}-sulfamic acid 6-(6-amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester 、 三氟乙酸 反应 2.0h， 以69%的产率得到[2-(6-hydroxy-benzothiazol-2-yl)-thiazole-4-carbonyl]-sulfamic acid 5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester trifluoroacetic acid salt
  参考文献：
  名称：

  Synthesis of an N-acyl sulfamate analog of luciferyl-AMP: A stable and potent inhibitor of firefly luciferase

  摘要：

  In the first of two half-reactions resulting in the emission of visible light, firefly luciferase forms luciferyl-adenylate from its natural substrates beetle luciferin and Mg-ATP. The acyl-adenylate is subsequently oxidized producing the light emitter oxyluciferin in an electronically excited state. In vitro, under mild conditions of temperature and pH, the acyl-adenylate intermediate is readily hydrolyzed and susceptible to oxidation. We report here the multi-step synthesis and physical and enzymatic characterization of an N-acyl sulfamate analog of luciferyi-adenylate, 5'-O-[(N-dehydroluciferyl)-sulfamoyl]-adenosine (compound 5). This represents the first example of a stable and potent (K-i = 340 nM) reversible inhibitor of firefly luciferase activity based on the structure of the natural acyl-adenylate intermediate. Additionally, we present the results of limited proteolysis studies that demonstrate that the binding of the novel acyl-adenylate analog protects luciferase from proteolysis. The findings presented here are interpreted in the context of the hypothesis that luciferase and the other enzymes in a large superfamily of adenylate-forming proteins adopt two conformations to catalyze two different partial reactions. We anticipate that the novel N-acyl sulfamate analog will be a valuable reagent in future studies designed to elucidate the role of conformational changes in firefly luciferase catalyzed bioluminescence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.115
• 作为产物：
  描述：

  2-[6-(2-methoxy-ethoxymethoxy)-benzothiazol-2-yl]-thiazole-4-carboxylic acid ethyl ester 在 lithium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 {2-[6-(2-methoxy-ethoxymethoxy)-benzothiazol-2-yl]-thiazole-4-carbonyl}-sulfamic acid 6-(6-amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester
  参考文献：
  名称：

  Synthesis of an N-acyl sulfamate analog of luciferyl-AMP: A stable and potent inhibitor of firefly luciferase

  摘要：

  In the first of two half-reactions resulting in the emission of visible light, firefly luciferase forms luciferyl-adenylate from its natural substrates beetle luciferin and Mg-ATP. The acyl-adenylate is subsequently oxidized producing the light emitter oxyluciferin in an electronically excited state. In vitro, under mild conditions of temperature and pH, the acyl-adenylate intermediate is readily hydrolyzed and susceptible to oxidation. We report here the multi-step synthesis and physical and enzymatic characterization of an N-acyl sulfamate analog of luciferyi-adenylate, 5'-O-[(N-dehydroluciferyl)-sulfamoyl]-adenosine (compound 5). This represents the first example of a stable and potent (K-i = 340 nM) reversible inhibitor of firefly luciferase activity based on the structure of the natural acyl-adenylate intermediate. Additionally, we present the results of limited proteolysis studies that demonstrate that the binding of the novel acyl-adenylate analog protects luciferase from proteolysis. The findings presented here are interpreted in the context of the hypothesis that luciferase and the other enzymes in a large superfamily of adenylate-forming proteins adopt two conformations to catalyze two different partial reactions. We anticipate that the novel N-acyl sulfamate analog will be a valuable reagent in future studies designed to elucidate the role of conformational changes in firefly luciferase catalyzed bioluminescence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.115