1-(2-deoxy-β-D-ribofuranosyl)benzimidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(2-deoxy-β-D-ribofuranosyl)benzimidazole
• 英文别名: benzimidazole-2'-deoxyriboside；(2R,3S,5R)-5-(1H-benzo[d]imidazol-1-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol；benzimidazole-2’-deoxyribose；(2R,3S,5R)-5-(benzimidazol-1-yl)-2-(hydroxymethyl)oxolan-3-ol
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: NBYVJYKXKSDSFB-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-β-D-ribofuranosyl)benzimidazole 在 吡啶 、 4-二甲氨基吡啶 、 4-羟基苯并三唑 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.25h， 生成 ((2R,3S,5R)-5-(1H-benzo[d]imidazol-1-yl)-3-hydroxytetrahydrofuran-2-yl)methyl triphosphate
  参考文献：
  名称：

  Specific Incorporation of an Artificial Nucleotide Opposite a Mutagenic DNA Adduct by a DNA Polymerase

  摘要：

  The ability to detect DNA modification sites at single base resolution could significantly advance studies regarding DNA adduct levels, which are extremely difficult to determine. Artificial nucleotides that are specifically incorporated opposite a modified DNA site offer a potential strategy for detection of such sites by DNA polymerase-based systems. Here we investigate the action of newly synthesized base-modified benzimidazole-derived 2'-deoxynucleoside-5'-O-triphosphates on DNA polymerases when performing translesion DNA synthesis past the pro-mutagenic DNA adduct O-6-benzylguanine (O6-BnG). We found that a mutated form of KlenTaq DNA polymerase, i.e., KTqM747K, catalyzed O6-BnG adduct-specific processing of the artificial BenziTP in favor of the natural dNTPs. Steady-state kinetic parameters revealed that KTqM747K catalysis of BenziTP is 25-fold more efficient for template O-6-BnG than G, and 5-fold more efficient than natural dTMP misincorporation in adduct bypass. Furthermore, the nucleotide analogue BenziTP is required for full-length product formation in O-6-BnG bypass, as without BenziTP the polymerase stalls at the adduct site. By combining the KTqM747K polymerase and BenziTP, a first round of DNA synthesis enabled subsequent amplification of Benzi-containing DNA. These results advance the development of technologies for detecting DNA adducts.

  DOI：

  10.1021/ja5100542
• 作为产物：
  描述：

  (2R,3S,5R)-5-(1H-benzo[d]imidazol-1-yl)-2-(((4-methylbenzoyl)oxy)methyl)tetrahydrofuran-3-yl 4-methylbenzoate 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 1-(2-deoxy-β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  氢键键合或堆叠相互作用，以区分含烷基化DNA的合成核苷探针的寡核苷酸的双链体稳定性。

  摘要：

  与修饰的DNA杂交的寡核苷酸是有用的化学工具，用于探测稳定DNA双链体的非共价相互作用。为了更好地理解影响杂交探针对O 6烷基鸟嘌呤损伤特异性的相互作用，我们就稳定由天然氨基酸组成的双链DNA的能力研究了一系列合成核苷类似物（BIM，Benzi和Peri）。或损坏的DNA寡核苷酸。碱基修饰的核苷类似物包含系统变化的氢键和π堆积性质。将核苷探针掺入DNA中并配对相反的规范碱基（A，T，C或G），O 6-甲基鸟嘌呤（O 6 -MeG），O6-苄基鸟嘌呤（O 6 -BnG）或稳定的无碱基位点类似物（四氢呋喃，THF）。根据双链体形成的自由能，当将Peri与O 6- MeG配对时，观察到最高的稳定度。热力学数据表明，较小的探针通过氢键使DNA双链体更稳定，而对π堆栈具有更大容量的较大的探针在碱基堆积的基础上对双链体的稳定做出了更大的贡献。这些结果表明，当BIM，Benzi或Peri与相反的含损伤DNA而不是未修饰的DNA（即O

  DOI：

  10.1002/chem.201204593

文献信息

• Enzymatic Synthesis of Therapeutic Nucleosides using a Highly Versatile Purine Nucleoside 2’‐DeoxyribosylTransferase from<i>Trypanosoma brucei</i>
  作者：Elena Pérez、Pedro A. Sánchez‐Murcia、Justin Jordaan、María Dolores Blanco、José Miguel Mancheño、Federico Gago、Jesús Fernández‐Lucas

  DOI：10.1002/cctc.201800775

  日期：2018.10.9

  selected as the best derivative (4200 IU/g, activity recovery of 22 %), and could be easily recaptured and recycled for >25 reactions with negligible loss of activity. Finally, MTbPDT3 was successfully employed in the expedient synthesis of several nucleoside analogues. Taken together, our results support the notion that TbPDT has good potential as an industrial biocatalyst for the synthesis of a wide range

  与多步化学方法相比，使用酶来合成核苷类似物具有多个优势，包括化学，区域和立体选择性以及较温和的反应条件。本文报道了来自布鲁氏锥虫的嘌呤核苷2'-脱氧核糖基转移酶（PDT）的生产，表征和利用。Tb PDT是一种二聚体，不仅在很宽的温度范围（50–70°C），pH（4–7）和离子强度（0–500 mM NaCl）范围内都显示出出色的活性和稳定性，而且在高温下具有非凡的高稳定性碱性条件（pH 8-10）。bPDT被证明可以熟练地合成许多治疗性核苷，包括去羟肌苷，维达拉滨，克拉屈滨，氟达拉滨和奈拉拉滨。用Ala或Ser进行结构指导的Val11置换，导致变体的活性提高了2.8倍。Tb PDT也共价固定在戊二醛激活的磁性微球上。选择了M Tb PDT3作为最佳衍生物（4200 IU / g，活性回收率为22％），可以轻松地将其重新捕获和再循环用于> 25个反应，而活性损失可忽略不计。最后，男铽PDT3
• Introduction of pseudo-base benzimidazole derivatives into nucleosides via base exchange by a nucleoside metabolic enzyme
  作者：Akihiko Hatano、Riki Matsuzaka、Genki Shimane、Hiroyuki Wakana、Kou Suzuki、Chisato Nishioka、Aoi Kojima、Masatoshi Kidowaki

  DOI：10.1016/j.bmc.2023.117411

  日期：2023.8

  organic synthesis, biocatalysis using enzymes provides a more stereoselective and cost-effective approach. Synthesis of unnatural nucleosides by nucleoside base exchange reactions using nucleoside-metabolizing enzymes has previously shown that the 5-position recognition of pyrimidine bases on nucleoside substrates is loose and can be used to introduce functional molecules into pyrimidine nucleosides. Here

  在替代有机合成中，使用酶的生物催化提供了一种更具立体选择性和成本效益的方法。使用核苷代谢酶通过核苷碱基交换反应合成非天然核苷先前表明，核苷底物上嘧啶碱基的5位识别是松散的，可用于将功能分子引入嘧啶核苷中。在这里，我们探索了通过嘧啶核苷磷酸化酶（PyNP）的碱基交换反应将嘌呤假碱基掺入核苷中，证明咪唑五元环是该反应的必要结构。就苯并咪唑而言，碱基交换产生脱氧核糖形式，产率 96%，核糖形式，产率 23%。该反应还用 1 H-咪唑并[4,5-b]吩嗪（一种带有附加环的苯并咪唑类似物）进行，尽管核苷的产率仅为 31%。1 H和咪唑并[4,5-b]吩嗪核苷与 PyNP (PDB 1BRW) 活性位点之间的对接模拟H-咪唑并[4,5-b]吩嗪可以用作 PyNP 的底物。因此，使用PyNP的酶促取代反应可用于将许多嘌呤假碱基和具有各种官能团的苯并咪唑衍生物掺入核苷结构中，其具有作为诊断或治疗剂的潜在用途。
• <i>Aeromonas hydrophila</i>strains as biocatalysts for transglycosylation
  作者：Matías Nóbile、Marco Terreni、Elizabeth Lewkowicz、Adolfo M. Iribarren

  DOI：10.3109/10242422.2010.538949

  日期：2010.12

  Microbial transglycosylation is useful as a green alternative in the preparation of purine nucleosides and analogues, especially for those that display pharmacological activities. In a search for new transglycosylation biocatalysts, two Aeromonas hydrophila strains were selected. The substrate specificity of both micro-organisms was studied and, as a result, several nucleoside analogues have been prepared. Among them, ribavirin, a broad spectrum antiviral, and the well-known anti HIV didanosine, were prepared, in 77 and 62% yield using A. hydrophila CECT 4226 and A. hydrophila CECT 4221, respectively. In order to scale-up the processes, the reaction conditions, product purification and biocatalyst preparation were analyzed and optimized.
• Use of Citrobacter koseri whole cells for the production of arabinonucleosides: A larger scale approach
  作者：Matías Nóbile、Rosario Médici、Marco Terreni、Elizabeth S. Lewkowicz、Adolfo M. Iribarren

  DOI：10.1016/j.procbio.2012.08.011

  日期：2012.12

  Purine arabinosides are well known antiviral and antineoplastic drugs. Since their chemical synthesis is complex, time-consuming, and polluting, enzymatic synthesis provides an advantageous alternative. In this work, we describe the microbial whole cell synthesis of purine arabinosides through nucleoside phosphorylase-catalyzed transglycosylation starting from their pyrimidine precursors. By screening of our microbial collection, Citrobacter koseri (CECT 856) was selected as the best biocatalyst for the proposed biotransformation. In order to enlarge the scale of the transformations to 150 mL for future industrial applications, the biocatalyst immobilization by entrapment techniques and its behavior in different reactor configurations, considering both batch and continuous processes, were analyzed. C koseri immobilized in agarose could be used up to 68 times and the storage stability was at least 9 months. By this approach, fludarabine (58% yield in 14h), vidarabine (71% yield in 26h) and 2,6-diaminopurine arabinoside (77% yield in 24h), were prepared. (C) 2012 Elsevier Ltd. All rights reserved.
• Tolerance of Base Pair Size and Shape in Postlesion DNA Synthesis
  作者：Hailey L. Gahlon、W. Bernd Schweizer、Shana J. Sturla

  DOI：10.1021/ja311434s

  日期：2013.5.1

  The influence of base pair size and shape on the fidelity of DNA polymerase-mediated extension past lesion-containing mispairs was examined. Primer extension analysis was performed with synthetic nucleo-sides paired opposite the pro-mutagenic DNA lesion O-6-benzylguanine (O-6-BnG). These data,indicate that the error prone DNA polymerase IV (Dpo4) inefficiently extended past the larger Peri:O-6-BnG base pair, and in contrast, error free extension was observed for the smaller BIM:O-6-BnG base pair. Steady-state kinetic analysis, revealed that Dpo4 catalytic efficiency was strongly influenced by the primer:template base pair. Compared to the C:G pair, a 1.9- and 79 000-fold reduction in Dpo4 efficiency was observed for terminal C:O-6-BnG and BIM:G base pairs respectively. These results demonstrate the impact of geometrical size and shape on polymerase-mediated mispair extension.