2-chloro-6-(3-methyl-2-butenyloxy)-9-(β-D-ribofuranosyl)purine | 65400-39-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-chloro-6-(3-methyl-2-butenyloxy)-9-(β-D-ribofuranosyl)purine
• 英文别名: (2R,3R,4S,5R)-2-[2-chloro-6-(3-methylbut-2-enylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 65400-39-7
• 化学式: C₁₅H₂₀ClN₅O₄
• 分子量: 369.808
• InChiKey: AZELFNACVPNYND-IDTAVKCVSA-N

物化性质

• 熔点：
  148-150 °C
• 沸点：
  632.9±65.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-chloro-6-(3-methyl-2-butenyloxy)-9-(β-D-ribofuranosyl)purine 在 Salmonella typhimurium O₂-dependent tRNA modifying monooxgenase 、 双氧水 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成
  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：

  (2-chloro-7(9)H-purin-6-yl)-(3-methyl-but-2-enyl)-amine 在 甲醇 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 2-chloro-6-(3-methyl-2-butenyloxy)-9-(β-D-ribofuranosyl)purine
  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

• Synthesis and evaluation of in vitro anticancer activity of some novel isopentenyladenosine derivatives
  作者：Roberta Ottria、Silvana Casati、Ada Manzocchi、Erika Baldoli、Massimo Mariotti、Jeanette A.M. Maier、Pierangela Ciuffreda

  DOI：10.1016/j.bmc.2010.04.093

  日期：2010.6.15

  and elemental analysis. We here show that only two derivatives, 1-(3-methyl-2-butenylamino)-9-(3′-deoxy-β-d-ribofuranosyl)-purine hydrobromide and 2-amino-6-(3-methyl-2- butenylamino)-9-(β-d-ribofuranosyl)-purine, inhibit the growth of T24 cells, although to a lower extent than N6-isopentenyladenosine. We conclude that the integrity of ribosidic and purine moiety and the N6 position of the chain are essential

  本研究描述了N 6-异戊烯基腺苷在T24人膀胱癌细胞上的某些衍生物的合成，表征和评价。特别地，我们已经修饰了核糖部分中的羟基，嘌呤环中异戊烯基链的位置和碱基部分。通过NMR，MS和元素分析的标准研究确认了化合物的结构。我们在这里显示只有两个衍生物，1-（3-甲基-2-丁烯基氨基）-9-（3'-脱氧-β- d-核呋喃糖基）-嘌呤氢溴酸盐和2-氨基-6-（3-甲基-2） -丁烯基氨基）-9-（β- d-核呋喃糖基）-嘌呤抑制T24细胞的生长，尽管程度低于N 6-异戊烯基腺苷。我们得出结论，核糖和嘌呤部分的完整性以及链的N 6位置对于维持抗增殖活性至关重要。
• 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: