(2S,3R,4S,5R)-2-(5,6-二甲基苯并咪唑-1-基)-5-(羟基甲基)四氢呋喃-3,4-二醇 | 132-13-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 苯并咪唑核糖核苷和核糖核苷酸
• 中文名称: (2S,3R,4S,5R)-2-(5,6-二甲基苯并咪唑-1-基)-5-(羟基甲基)四氢呋喃-3,4-二醇
• 中文别名: α-核唑
• 英文名称: 5,6-dimethyl-α-D-ribofuranosylbenzimidazole
• 英文别名: N1-(alpha-D-ribosyl)-5,6-dimethyl-benzimidazole；α-ribazole；1-(5,6-dimethyl-benzoimidazol-1-yl)-α-D-1-deoxy-ribofuranose；5,6-Dimethyl-1-α-D-ribofuranosyl-1H-benzimidazol；5,6-Dimethyl-1-α-D-ribofuranosyl-benzimidazol od. α-Ribazol；Ribazol；alpha-Ribazole；(2S,3R,4S,5R)-2-(5,6-dimethylbenzimidazol-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 132-13-8
• 化学式: C₁₄H₁₈N₂O₄
• 分子量: 278.308
• InChiKey: HLRUKOJSWOKCPP-SYQHCUMBSA-N

物化性质

• 熔点：
  198-199°
• 比旋光度：
  D23 +14° (c = 0.9 in pyridine)
• 沸点：
  569.2±60.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  adenosylcob(III)inamide-GDP 、 (2S,3R,4S,5R)-2-(5,6-二甲基苯并咪唑-1-基)-5-(羟基甲基)四氢呋喃-3,4-二醇 生成 adenosylcob(III)alamin 、 guanosine 5'-monophosphate 、 氢(+1)阳离子
  参考文献：
  名称：

  鼠伤寒沙门氏菌酶体外合成钴胺素核苷酸环。

  摘要：

  在鼠伤寒沙门氏菌中，已提出了CobU，CobS，CobT和CobC蛋白来催化腺苷钴胺素生物合成的后期步骤，后者定义了核苷酸环组装途径。本文报道了腺苷钴胺素的前体腺苷钴胺，5，6-二甲基苯并咪唑，烟酸酯单核苷酸和GTP的核苷酸环的体外组装。这些前体与CobU，CobS和CobT蛋白一起孵育可合成腺苷钴胺素5'-磷酸。通过HPLC分离该钴酰胺，通过UV-可见光谱和质谱鉴定，并显示出支持钴胺素营养缺陷型的生长。腺苷钴胺素-5'-磷酸也从含有腺苷钴胺-GDP（CobU反应产物）和α-核唑-5'的反应混合物中分离出来。-磷酸盐（CobT反应的产物）作为底物和CobS。这些结果使我们可以得出结论，CobS是鼠伤寒沙门氏菌中的钴胺素（-5'-磷酸）合酶。以前显示出将CobC酶将α-核唑5'-磷酸脱磷酸为α-核唑，显示为将腺苷钴胺素5'-磷酸脱磷酸为腺苷钴胺素。在反应混合物中所有四种酶均存在的反应中，腺苷

  DOI：

  10.1073/pnas.96.21.11798
• 作为产物：
  描述：

  5-O-三苯甲基-2,3-O-异亚丙基-D-呋喃核糖 在 2-fluoro-methylpyridinium tosylate 、 四溴化碳 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 (2S,3R,4S,5R)-2-(5,6-二甲基苯并咪唑-1-基)-5-(羟基甲基)四氢呋喃-3,4-二醇
  参考文献：
  名称：

  Deprotection of α-imidazole/benzimidazole ribonucleosides by catalytic carbon tetrabromide initiated photolysis

  摘要：

  Several protected benzimidazole and imidazole alpha-ribonucleosides were deprotected in excellent yield Lit ambient temperature using CBr4 initiated photolysis in methanol at ambient temperature. No selectivity was observed and both trityl and isopropylidene groups were deprotected Under the reaction conditions. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.09.180

文献信息

• <i>In vitro</i> synthesis of the nucleotide loop of cobalamin by <i>Salmonella typhimurium</i> enzymes
  作者：Lori A. Maggio-Hall、Jorge C. Escalante-Semerena

  DOI：10.1073/pnas.96.21.11798

  日期：1999.10.12

  reaction) as substrates and CobS. These results allowed us to conclude that CobS is the cobalamin(-5'-phosphate) synthase enzyme in S. typhimurium. The CobC enzyme, previously shown to dephosphorylate alpha-ribazole-5'-phosphate to alpha-ribazole, was shown to dephosphorylate adenosylcobalamin-5'-phosphate to adenosylcobalamin. Adenosylcobinamide was converted to adenosylcobalamin in reactions where all

  在鼠伤寒沙门氏菌中，已提出了CobU，CobS，CobT和CobC蛋白来催化腺苷钴胺素生物合成的后期步骤，后者定义了核苷酸环组装途径。本文报道了腺苷钴胺素的前体腺苷钴胺，5，6-二甲基苯并咪唑，烟酸酯单核苷酸和GTP的核苷酸环的体外组装。这些前体与CobU，CobS和CobT蛋白一起孵育可合成腺苷钴胺素5'-磷酸。通过HPLC分离该钴酰胺，通过UV-可见光谱和质谱鉴定，并显示出支持钴胺素营养缺陷型的生长。腺苷钴胺素-5'-磷酸也从含有腺苷钴胺-GDP（CobU反应产物）和α-核唑-5'的反应混合物中分离出来。-磷酸盐（CobT反应的产物）作为底物和CobS。这些结果使我们可以得出结论，CobS是鼠伤寒沙门氏菌中的钴胺素（-5'-磷酸）合酶。以前显示出将CobC酶将α-核唑5'-磷酸脱磷酸为α-核唑，显示为将腺苷钴胺素5'-磷酸脱磷酸为腺苷钴胺素。在反应混合物中所有四种酶均存在的反应中，腺苷
• Structural and Functional Characterization of an RNase HI Domain from the Bifunctional Protein Rv2228c from <i>Mycobacterium tuberculosis</i>
  作者：Harriet A. Watkins、Edward N. Baker

  DOI：10.1128/jb.01615-09

  日期：2010.6

  The open reading frame Rv2228c from Mycobacterium tuberculosis is predicted to encode a protein composed of two domains, each with individual functions, annotated through sequence similarity searches. The N-terminal domain is homologous with prokaryotic and eukaryotic RNase H domains and the C-terminal domain with α-ribazole phosphatase (CobC). The N-terminal domain of Rv2228c (Rv2228c/N) and the full-length protein were expressed as fusions with maltose binding protein (MBP). Rv2228c/N was shown to have RNase H activity with a hybrid RNA/DNA substrate as well as double-stranded RNase activity. The full-length protein was shown to have additional CobC activity. The crystal structure of the MBP-Rv2228c/N fusion protein was solved by molecular replacement and refined at 2.25-Å resolution ( R = 0.182; R _free = 0.238). The protein is monomeric in solution but associates in the crystal to form a dimer. The Rv2228c/N domain has the classic RNase H fold and catalytic machinery but lacks several surface features that play important roles in the cleavage of RNA/DNA hybrids by other RNases H. The absence of either the basic protrusion of some RNases H or the hybrid binding domain of others appears to be compensated by the C-terminal CobC domain in full-length Rv2228c. The double-stranded-RNase activity of Rv2228c/N contrasts with classical RNases H and is attributed to the absence in Rv2228c/N of a key phosphate binding pocket.

  摘要 结核分枝杆菌的开放阅读框 Rv2228c 结核分枝杆菌 的开放阅读框 Rv2228c 预测编码一种由两个结构域组成的蛋白质，每个结构域都有各自的功能，并通过序列相似性搜索进行了注释。N 端结构域与原核生物和真核生物的 RNase H 结构域同源，而 C 端结构域则与α-核唑磷酸酶（CobC）同源。Rv2228c 的 N 端结构域（Rv2228c/N）和全长蛋白质与麦芽糖结合蛋白（MBP）融合表达。研究表明，Rv2228c/N 具有 RNA/DNA 混合底物的 RNase H 活性以及双链 RNase 活性。全长蛋白还具有额外的 CobC 活性。MBP-Rv2228c/N 融合蛋白的晶体结构是通过分子置换解决的，并以 2.25 Å 的分辨率精制而成 ( R = 0.182; R free = 0.238).该蛋白在溶液中是单体，但在晶体中会结合形成二聚体。Rv2228c/N 结构域具有典型的 RNase H 折叠和催化机制，但缺乏在其他 RNase H 裂解 RNA/DNA 杂交体时发挥重要作用的几个表面特征。Rv2228c/N 的双链 RNase 活性与经典 RNase H 形成了鲜明对比，这是因为 Rv2228c/N 中缺少一个关键的磷酸盐结合口袋。
• Reassessment of the Late Steps of Coenzyme B ₁₂ Synthesis in <i>Salmonella enterica</i> : Evidence that Dephosphorylation of Adenosylcobalamin-5′-Phosphate by the CobC Phosphatase Is the Last Step of the Pathway
  作者：Carmen L. Zayas、Jorge C. Escalante-Semerena

  DOI：10.1128/jb.01665-06

  日期：2007.3.15

  We report that cobC strains of Salmonella enterica serovar Typhimurium are impaired in the ability to salvage cobyric acid (Cby), a de novo corrin ring biosynthetic intermediate, under aerobic growth conditions. In vivo and in vitro evidence support the conclusion that this new phenotype of cobC strains is due to the inability of serovar Typhimurium to dephosphorylate adenosylcobalamin-5′-phosphate (AdoCbl-5′-P), the product of the condensation of α-ribazole-5′-phosphate (α-RP) and adenosylcobinamide-GDP by the AdoCbl-5′-P synthase (CobS, EC 2.7.8.26) enzyme. Increased flux through the 5,6-dimethylbenzimidazole and cobinamide (Cbi) activation branches of the nucleotide loop assembly pathway in cobC strains restored AdoCbl-5′-P synthesis from Cby in a cobC strain. The rate of the CobS-catalyzed reaction was at least 2 orders of magnitude higher with α-RP than with α-ribazole as substrate. On the basis of the data reported herein, we conclude that removal of the phosphoryl group from AdoCbl-5′-P is the last step in AdoCbl biosynthesis in serovar Typhimurium and that the reaction is catalyzed by the AdoCbl-5′-P phosphatase (CobC) enzyme. Explanations for the correction of the Cby salvaging phenotype are discussed.

  摘要 我们报告了 cobC 菌株的 肠炎沙门氏菌 血清伤寒沙门氏菌的 cobC 菌株在有氧生长条件下挽救从头开始的珊瑚酸环生物合成中间体 cobyric acid (Cby) 的能力受损。体内和体外证据都支持这样的结论，即这种新的 cobC 菌株的这一新表型是由于 Typhimurium 血清不能通过 AdoCbl-5′-P 合成酶（CobS，EC 2.7.8.26）酶。通过核苷酸环组装途径的 5,6-二甲基苯并咪唑和钴酰胺（Cbi）活化分支的通量在 cobC 菌株中通过 5,6-二甲基苯并咪唑和钴氨酰胺（Cbi）激活核苷酸环组装途径分支的通量增加，恢复了 Cby 在 cobC 菌株中 Cby 的 AdoCbl-5′-P 合成。以 α-RP 为底物的 CobS 催化反应速率比以 α-ribazole 为底物的 CobS 催化反应速率至少高 2 个数量级。根据本文报告的数据，我们得出结论：从 AdoCbl-5′-P 中去除磷酸基是 Typhimurium 血清中 AdoCbl 生物合成的最后一步，该反应由 AdoCbl-5′-P 磷酸酶（CobC）催化。讨论了纠正 Cby 挽救表型的原因。
• Probe compound for detecting and isolating enzymes and means and methods using the same
  申请人：Helmholtz-Zentrum für Infektionsforschung GmbH

  公开号：EP2230312A1

  公开（公告）日：2010-09-22

  The present invention relates to a probe compound that can comprise any substrate or metabolite of an enzymatic reaction in addition to an indicator component, such as, for example, a fluorescence dye, or the like. Moreover, the present invention relates to means for detecting enzymes in form of an array, which comprises any number of probe compounds of the invention which each comprise a different metabolite of interconnected metabolites representing the central pathways in all forms of life. Moreover, the present invention relates to a method for detecting enzymes involving the application of cell extracts or the like to the array of the invention which leads to reproducible enzymatic reactions with the substrates. These specific enzymatic reactions trigger the indicator (e.g. a fluorescence signal) and bind the enzymes to the respective cognate substrates. Moreover, the invention relates to means for isolating enzymes in form of nanoparticles coated with the probe compound of the invention. The immobilisation of the cognate substrates or metabolites on the surface of nanoparticles by means of the probe compounds allows capturing and isolating the respective enzyme, e.g. for subsequent sequencing.

  本发明涉及一种探针化合物，它可以包括酶反应的任何底物或代谢物，此外还包括指示成分，例如荧光染料或类似物。此外，本发明还涉及以阵列形式检测酶的方法，该阵列由任意数量的本发明探针化合物组成，每种探针化合物由代表所有生命形式中中心途径的相互关联的代谢物中的不同代谢物组成。此外，本发明还涉及一种检测酶的方法，该方法涉及将细胞提取物或类似物应用于本发明的阵列，从而导致与底物发生可重复的酶反应。这些特定的酶反应会触发指示剂（如荧光信号），并将酶与各自的同源底物结合。此外，本发明还涉及以涂覆有本发明探针化合物的纳米颗粒形式分离酶的方法。通过探针化合物将同源底物或代谢物固定在纳米颗粒表面，可以捕获和分离相应的酶，例如用于后续测序。
• CELL FACTORIES FOR IMPROVED PRODUCTION OF COMPOUNDS AND PROTEINS DEPENDENT ON IRON SULFUR CLUSTERS
  申请人：Biosyntia ApS

  公开号：EP3683227A1

  公开（公告）日：2020-07-22

  The invention relates to a genetically modified prokaryotic cell capable of improved iron-sulfur cluster delivery, characterized by a modified gene encoding a mutant Iron Sulfur Cluster Regulator (IscR) as well as one or more transgenes or upregulated endogenous genes encoding iron-sulfur (Fe-S) cluster polypeptides or proteins that catalyze complex radical-mediated molecular rearrangements, electron transfer, radical or non-redox reactions, sulfur donation or perform regulatory functions. Prokaryotic cells of the invention are characterized by enhanced activity of these iron-sulfur (Fe-S) cluster polypeptides, thereby enhancing their respective functional capacity, as well as facilitating enhanced yields of diverse compounds in free and protein-bound forms, including heme, hemoproteins, tetrapyrroles, B vitamins, amino acids, δ-aminolevulinic acid, biofuels, isoprenoids, pyrroloquinoline quinone, ammonia, indigo or their precursors, whose biosynthesis depends on their activity. The invention further relates to a method for producing each of said compounds, or their precursors using the genetically modified prokaryotic cell of the invention; as well as the use of the genetically modified prokaryotic cell.

  本发明涉及一种能够改善铁硫簇传递的转基因原核细胞，其特征是具有编码突变型铁硫簇调节器（IscR）的修饰基因以及一个或多个编码铁硫（Fe-S）簇多肽或蛋白质的转基因或上调内源基因，这些基因或蛋白质可催化复杂的自由基介导的分子重排、电子转移、自由基或非氧化还原反应、硫捐赠或执行调节功能。本发明原核细胞的特点是这些铁硫（Fe-S）簇多肽的活性增强，从而提高了它们各自的功能能力，并促进了游离和蛋白结合形式的多种化合物产量的提高、这些化合物包括血红素、血蛋白、四吡咯、B 族维生素、氨基酸、δ-氨基乙酰丙酸、生物燃料、异戊二烯、吡咯喹啉醌、氨、靛蓝或其前体，其生物合成取决于它们的活性。本发明还涉及使用本发明的转基因原核细胞生产上述每种化合物或其前体的方法；以及转基因原核细胞的使用。