(3-methyl-but-2-enyl)-(2-methylsulfanyl-7(9)H-purin-6-yl)-amine | 20758-33-2

• 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: (3-methyl-but-2-enyl)-(2-methylsulfanyl-7(9)H-purin-6-yl)-amine
• 英文别名: 6-(3-Methyl-2-butenylamino)-2-methylthiopurine；6-(3-Methyl-2-butenylamino)-2-methylthiopurin；N6-(Δ2-Isopentenyl)-2-methylthioadenin；N-(3-Methylbut-2-en-1-yl)-2-(methylsulfanyl)-7H-purin-6-amine；N-(3-methylbut-2-enyl)-2-methylsulfanyl-7H-purin-6-amine
• CAS: 20758-33-2
• 化学式: C₁₁H₁₅N₅S
• 分子量: 249.34
• InChiKey: VVJZYTNYVBSADL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-methyl-but-2-enyl)-(2-methylsulfanyl-7(9)H-purin-6-yl)-amine 在 甲醇 、 三氟甲磺酸三甲基硅酯 、 Salmonella typhimurium O₂-dependent tRNA modifying monooxgenase 、 双氧水 、 sodium methylate 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 25.0h， 生成 N⁶-(4-hydroxy-3-methyl-but-2-enyl)-S-methyl-2-thio-isoguanosine
  参考文献：
  名称：

  Peroxide-Shunt Substrate-Specificity for the Salmonella typhimurium O₂-Dependent tRNA Modifying Monooxygenase (MiaE)

  摘要：

  Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O-2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl-adenosine(37)-tRNA) [designated ms(2)i(6)A(37)]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) and their corresponding hydroxylated products (io(6)A, Cl(2)io(6)A, and ms(2)io(6)A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v(0)/[E] for ms(2)i(6)A > i(6)A > Cl(2)i(6)A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms(2)i(6)A nucleoside relative to i(6)A is consistent with previous whole cell assays reporting the ms(2)io(6)A and io(6)A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity:

  DOI：

  10.1021/bi4000832
• 作为产物：
  描述：

  6-硫代-2-羟基嘌呤 在 potassium carbonate 作用下， 以 正丁醇 为溶剂， 反应 5.0h， 生成 (3-methyl-but-2-enyl)-(2-methylsulfanyl-7(9)H-purin-6-yl)-amine
  参考文献：
  名称：

  Peroxide-Shunt Substrate-Specificity for the Salmonella typhimurium O₂-Dependent tRNA Modifying Monooxygenase (MiaE)

  摘要：

  Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O-2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl-adenosine(37)-tRNA) [designated ms(2)i(6)A(37)]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) and their corresponding hydroxylated products (io(6)A, Cl(2)io(6)A, and ms(2)io(6)A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v(0)/[E] for ms(2)i(6)A > i(6)A > Cl(2)i(6)A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms(2)i(6)A nucleoside relative to i(6)A is consistent with previous whole cell assays reporting the ms(2)io(6)A and io(6)A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity:

  DOI：

  10.1021/bi4000832

文献信息

• Peroxide-Shunt Substrate-Specificity for the Salmonella typhimurium O₂-Dependent tRNA Modifying Monooxygenase (MiaE)
  作者：Andra L. Corder、Bishnu P. Subedi、Siai Zhang、Amanda M. Dark、Frank W. Foss、Brad S. Pierce

  DOI：10.1021/bi4000832

  日期：2013.9.10

  Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O-2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl-adenosine(37)-tRNA) [designated ms(2)i(6)A(37)]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) and their corresponding hydroxylated products (io(6)A, Cl(2)io(6)A, and ms(2)io(6)A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v(0)/[E] for ms(2)i(6)A > i(6)A > Cl(2)i(6)A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms(2)i(6)A nucleoside relative to i(6)A is consistent with previous whole cell assays reporting the ms(2)io(6)A and io(6)A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity: