methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate | 933447-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate
• CAS: 933447-90-6
• 化学式: C₁₅H₁₆N₂O₇
• 分子量: 336.301
• InChiKey: NFGXRGGPQDWBEQ-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.98
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  124.06
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 methyl 1-(3-O-{[(2-cyanoethoxy)(diisopropylamino)phosphonyl]oxy}-2-deoxy-5-O-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate
  参考文献：
  名称：

  Effect of a Hydrogen Bonding Carboxamide Group on Universal Bases

  摘要：

  文献中描述了许多芳香族通用碱基模拟物，但大多数都不具有氢键结合作用。我们研究了在5-硝基吲哚的吡咯环上引入氢键结合羧酰胺基团的效果。修改后的类似物保留了通用碱基的特征，但对双链稳定性没有总体影响。这表明硝基基团在双链的氢键面内，而氢键结合的羧酰胺基团位于双链的主沟槽中。

  DOI：

  10.1135/cccc20060899
• 作为产物：
  描述：

  5-硝基吲哚-3-甲酸 在 硫酸 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 24.5h， 生成 methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate
  参考文献：
  名称：

  Effect of a Hydrogen Bonding Carboxamide Group on Universal Bases

  摘要：

  文献中描述了许多芳香族通用碱基模拟物，但大多数都不具有氢键结合作用。我们研究了在5-硝基吲哚的吡咯环上引入氢键结合羧酰胺基团的效果。修改后的类似物保留了通用碱基的特征，但对双链稳定性没有总体影响。这表明硝基基团在双链的氢键面内，而氢键结合的羧酰胺基团位于双链的主沟槽中。

  DOI：

  10.1135/cccc20060899

文献信息

• WO2007/135380
  申请人：——

  公开号：——

  公开（公告）日：——
• Evolving a Polymerase for Hydrophobic Base Analogues
  作者：David Loakes、José Gallego、Vitor B. Pinheiro、Eric T. Kool、Philipp Holliger

  DOI：10.1021/ja9039696

  日期：2009.10.21

  Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene phi (abasic site), d5NI phi, and isocarbostyril (ICS). 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity