methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate 5'-triphosphate | 1190093-05-0

• 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 5'-triphosphate
• CAS: 1190093-05-0
• 化学式: C₁₅H₁₉N₂O₁₆P₃
• 分子量: 576.241
• InChiKey: SQABYMLHAPGVSD-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.33
• 重原子数：
  36.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  263.65
• 氢给体数：
  5.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate 5'-triphosphate 在 氨 作用下， 生成 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxamide 5'-triphosphate
  参考文献：
  名称：

  Evolving a Polymerase for Hydrophobic Base Analogues

  摘要：

  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

  DOI：

  10.1021/ja9039696
• 作为产物：
  描述：

  methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate 在 磷酸三甲酯 、 Proton Sponge 、 三氯氧磷 、 pyrophosphate tetrabutylammonium salt 、 三正丁胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 methyl 1-(2-deoxy-β-D-ribofuranosyl)-5-nitroindole-3-carboxylate 5'-triphosphate
  参考文献：
  名称：

  Evolving a Polymerase for Hydrophobic Base Analogues

  摘要：

  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

  DOI：

  10.1021/ja9039696