[5-(5-氨基咪唑-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基膦酸 | 25635-88-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: [5-(5-氨基咪唑-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基膦酸
• 英文名称: 5-aminoimidazole ribonucleotide
• 英文别名: AIR；1-<β-D-5-Phosphoribosyl>-5-amino-imidazol；[(2R,3S,4R,5R)-5-(5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 25635-88-5
• 化学式: C₈H₁₄N₃O₇P
• 分子量: 295.189
• InChiKey: PDACUKOKVHBVHJ-XVFCMESISA-N

物化性质

• 沸点：
  774.0±70.0 °C(Predicted)
• 密度：
  2.16±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [5-(5-氨基咪唑-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基膦酸 在 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase 作用下， 生成 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate
  参考文献：
  名称：

  The Thiamine Biosynthetic Enzyme ThiC Catalyzes Multiple Turnovers and Is Inhibited by S-Adenosylmethionine (AdoMet) Metabolites

  摘要：

  ThiC (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase; EC 4.1.99.17) is a radical S-adenosylmethionine (AdoMet) enzyme that uses a [4Fe-4S](+) cluster to reductively cleave AdoMet to methionine and a 5-deoxyadenosyl radical that initiates catalysis. In plants and bacteria, ThiC converts the purine intermediate 5-aminoimidazole ribotide to 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate, an intermediate of thiamine pyrophosphate (coenzyme B1) biosynthesis. In this study, assay conditions were implemented that consistently generated 5-fold molar excess of HMP, demonstrating that ThiC undergoes multiple turnovers. ThiC activity was improved by in situ removal of product 5-deoxyadenosine. The activity was inhibited by AdoMet metabolites S-adenosylhomocysteine, adenosine, 5-deoxyadenosine, S-methyl-5-thioadenosine, methionine, and homocysteine. Neither adenosine nor S-methyl-5-thioadenosine had been shown to inhibit radical AdoMet enzymes, suggesting that ThiC is distinct from other family members. The parameters for improved ThiC activity and turnover described here will facilitate kinetic and mechanistic analyses of ThiC.

  DOI：

  10.1074/jbc.m113.500280
• 作为产物：
  描述：

  2,3,5-tri-O-acetyl-D-ribofuranosyl bromide 在 potassium dihydrogenphosphate 、 palladium 10% on activated carbon 、 氨 、 氢气 、 AIRs kinase 、 5’-三磷酸腺苷 作用下， 以 甲醇 、 aq. phosphate buffer 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 30.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成 [5-(5-氨基咪唑-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基膦酸
  参考文献：
  名称：

  采用新型弗里德尔-克来福特酰基转移酶的 4-酰基-5-氨基咪唑生物碱的生物合成

  摘要：

  弗里德尔-克来福特酰化 (FCA) 是有机化学中一种非常有益的方法，用于创建重要的 C-C 键，这些键是在芳香底物和酰基之间构建复杂框架所必需的。然而，关于酶催化FCA反应的报道很少。在本研究中，4-酰基-5-氨基咪唑生物碱 (AAIA)、链咪唑 A–C ( 1 – 3 ) 和对映体纯 (+)-诺卡咪唑 C ( 4 ) 及其核苷、链咪唑苷 A–D ( 5 – 8 )，从链霉菌的发酵液中鉴定出来。 OUCMDZ-944 或异源天蓝色链球菌M1154 突变体。鉴定了生物合成基因簇( smz )，首次阐明了AAIA的生物合成途径。体内和体外研究证明了四个必需基因smzB 、 -C 、 -E和-F对AAIA生物合成的催化活性，并阐明了生物碱的生物合成过程。连接酶 SmzE 激活脂肪酰基并将其连接到酰基载体蛋白 (ACP) Holo-SmzF。然后，酰基被转移到 SmzB 的关键残基 Cys49 上，SmzB

  DOI：

  10.1021/jacs.3c09522

文献信息

• Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B₁₂ Biosynthesis
  作者：Angad P. Mehta、Sameh H. Abdelwahed、Michael K. Fenwick、Amrita B. Hazra、Michiko E. Taga、Yang Zhang、Steven E. Ealick、Tadhg P. Begley

  DOI：10.1021/jacs.5b03576

  日期：2015.8.26

  (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving

  细菌硫胺嘧啶合酶 (thiC) 的比较基因组学揭示了 thiC (bzaF) 的旁系同源物与厌氧维生素 B12 生物合成基因聚集在一起。在此，我们证明 BzaF 是一种自由基 S-腺苷甲硫氨酸酶，可催化氨基咪唑核苷酸 (AIR) 显着转化为 5-羟基苯并咪唑 (5-HBI)。我们确定了关键产物原子的起源并提出了反应机制。这些研究代表了解决厌氧维生素 B12 组装中长期存在的问题的第一步，并揭示了硫胺素和维生素 B12 生物合成的意外交叉。
• Methods for indentifying compounds that modulate an enzyme in the coenzyme a biosynthetic pathway in a pathogenic microoganism
  申请人：Schechter M. Alan

  公开号：US20060094075A1

  公开（公告）日：2006-05-04

  A method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in a metabolic pathway by inhibiting the conversion of substrate to produce the penultimate or ultimate product particularly by inhibiting the activity of one or more of the enzymes in the pathway, and compounds and pharmaceutical compositions for inhibiting infections of pathogenic microorganisms by inhibiting such enzymes.

  一种通过抑制代谢途径中一个或多个酶的活性，抑制底物转化为产生次终产物或终产物的过程，特别是通过抑制途径中一个或多个酶的活性，来识别和治疗病原微生物感染的方法，以及用于抑制这些酶而抑制病原微生物感染的化合物和药物组合物。
• Method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in an essential metabolic pathway
  申请人：Pyro Pharmaceuticals, Inc.

  公开号：US20030180830A1

  公开（公告）日：2003-09-25

  A method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in a metabolic pathway by inhibiting the conversion of substrate to produce the penultimate or ultimate product particularly by inhibiting the activity of one or more of the enzymes in the pathway

  一种通过抑制代谢途径中一个或多个酶的活性，从而抑制底物转化产生次终产物或最终产物，特别是通过抑制代谢途径中一个或多个酶的活性来识别和治疗病原微生物感染的方法。
• Method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in an essential metabolic pathway and compounds and pharmaceutical compositions useful therefor
  申请人：Pyro Pharmaceuticals, Inc.

  公开号：US20040006040A1

  公开（公告）日：2004-01-08

  A method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in a metabolic pathway by inhibiting the conversion of substrate to produce the penultimate or ultimate product particularly by inhibiting the activity of one or more of the enzymes in the pathway, and compounds and pharmaceutical compositions for inhibiting infections of pathogenic microorganisms by inhibiting such enzymes.

  一种通过抑制代谢途径中的一个或多个酶，抑制底物转化为产生次终产物或终产物的方法，特别是通过抑制途径中一个或多个酶的活性，用于鉴定和治疗病原微生物感染，以及用于抑制这些酶的化合物和制药组合物，用于抑制病原微生物感染。
• Methods for indentifying compounds that modulate an enzyme involved in reductive carboxylation in a pathogenic microorganism
  申请人：Schechter M. Alan

  公开号：US20060178321A1

  公开（公告）日：2006-08-10

  A method for the identification and treatment of pathogenic microorganism infections by inhibiting one or more enzymes in a metabolic pathway by inhibiting the conversion of substrate to produce the penultimate or ultimate product particularly by inhibiting the activity of one or more of the enzymes in the pathway, and compounds and pharmaceutical compositions for inhibiting infections of pathogenic microorganisms by inhibiting such enzymes.

  一种通过抑制代谢途径中的一个或多个酶来抑制底物转化为产生次终产物或终产物的方法，特别是通过抑制途径中一个或多个酶的活性，用于鉴定和治疗病原微生物感染，以及用于抑制这些酶的化合物和制药组合物以抑制病原微生物感染的方法。