2'-deoxyguanosine 5'-(α,β-imido)triphosphate

• 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'-deoxyguanosine 5'-(α,β-imido)triphosphate
• 英文别名: 2'-Deoxy-5'-O-[(R)-Hydroxy{[(R)-Hydroxy(Phosphonooxy)phosphoryl]amino}phosphoryl]guanosine；[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-N-[hydroxy(phosphonooxy)phosphoryl]phosphonamidic acid
• 化学式: C₁₀H₁₇N₆O₁₂P₃
• 分子量: 506.199
• InChiKey: DWGAAFQEGIMTIA-KVQBGUIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  277
• 氢给体数：
  8
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  2'-脱氧鸟苷 在 sodium hydroxide 、 pyruvate kinase 、 磷酸三乙酯 、 磷烯醇丙酮酸 、 dichlorophosphinylphosphorimidic trichloride 、 potassium chloride 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 14.5h， 生成 2'-deoxyguanosine 5'-(α,β-imido)triphosphate
  参考文献：
  名称：

  Synthesis, Characterization, and Inhibitory Activities of Nucleoside α,β-Imido Triphosphate Analogues on Human Immunodeficiency Virus-1 Reverse Transcriptase

  摘要：

  Six deoxynucleoside triphosphate (dNTP) analogues were synthesized, having the alpha,beta-P-O-P bond replaced with an imido (P-N-P) functionality. They were all shown to be reasonably potent inhibitors of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT). This has permitted, for the first time, an estimate of the relative binding affinities of the parent triphosphates (dATP, TTP, dGTP, and dCTP) toward the enzyme's active site, in that they can be compared indirectly by correlation with the behavior of their alpha,beta-imido analogues. Other complicating processes such as consecutive incorporation into the growing DNA chain can be excluded because the imido linkage cannot be cleaved by HIV-1 RT. The 5-iodo analog of deoxyuridine triphosphate (IdUMPNPP, 5) was the most potent inhibitor, having an IC50 value of 7 mu M. A general route for the phosphorylation of purine and pyrimidine 5'-imidodiphosphates by pyruvate kinase was developed using phosphoenolpyruvate (PEP) as a phosphoryl group donor. Enzymatic phosphorylation was shown to be a more efficient approach than chemical methods. (C) 1996 Academic Press, Inc.

  DOI：

  10.1006/bioo.1996.0023

文献信息

• Synthesis, Characterization, and Inhibitory Activities of Nucleoside α,β-Imido Triphosphate Analogues on Human Immunodeficiency Virus-1 Reverse Transcriptase
  作者：Rongshi Li、Angelika Muscate、George L. Kenyon

  DOI：10.1006/bioo.1996.0023

  日期：1996.9

  Six deoxynucleoside triphosphate (dNTP) analogues were synthesized, having the alpha,beta-P-O-P bond replaced with an imido (P-N-P) functionality. They were all shown to be reasonably potent inhibitors of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT). This has permitted, for the first time, an estimate of the relative binding affinities of the parent triphosphates (dATP, TTP, dGTP, and dCTP) toward the enzyme's active site, in that they can be compared indirectly by correlation with the behavior of their alpha,beta-imido analogues. Other complicating processes such as consecutive incorporation into the growing DNA chain can be excluded because the imido linkage cannot be cleaved by HIV-1 RT. The 5-iodo analog of deoxyuridine triphosphate (IdUMPNPP, 5) was the most potent inhibitor, having an IC50 value of 7 mu M. A general route for the phosphorylation of purine and pyrimidine 5'-imidodiphosphates by pyruvate kinase was developed using phosphoenolpyruvate (PEP) as a phosphoryl group donor. Enzymatic phosphorylation was shown to be a more efficient approach than chemical methods. (C) 1996 Academic Press, Inc.