nicotinate D-ribonucleotide | 27260-32-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡啶核苷酸
• 英文名称: nicotinate D-ribonucleotide
• 英文别名: β-Nicotinamid-mononucleotid；Nicotinate mononucleotide；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]pyridin-1-ium-3-carboxylic acid
• CAS: 27260-32-8
• 化学式: C₁₁H₁₅NO₉P
• 分子量: 336.215
• InChiKey: JOUIQRNQJGXQDC-ZYUZMQFOSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  158
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (6-aminohexyl)triphenylphosphonium bromide 、 nicotinate D-ribonucleotide 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以Ca. 45 %的产率得到1-((2R,3R,4S,5R)-3,4-dihydroxy-5-((phosphonooxy)methyl)tetrahydrofuran-2-yl)-3-((6-(triphenylphosphonio)hexyl)carbamoyl)pyridin-1-ium
  参考文献：
  名称：

  NICOTINATE AND NICOTINAMIDE RIBOSIDE-BASED COMPOUNDS AND DERIVATIVES THEREOF

  摘要：

  Disclosed herein are compounds related to nicotinate and nicotinamide riboside and methods of making and using said compounds. Also disclosed herein are methods of making nicotinic acid mononucleoside (NAMN).

  公开号：

  US20230242558A1
• 作为产物：
  描述：

  2,3-吡啶二甲酸 、 PRPP 在 Salmonella typhimurium quinolinate phosphoribosyltransferase 、 magnesium chloride 作用下， 生成 nicotinate D-ribonucleotide
  参考文献：
  名称：

  Interactions at the 2 and 5 Positions of 5-Phosphoribosyl Pyrophosphate Are Essential in Salmonella typhimurium Quinolinate Phosphoribosyltransferase

  摘要：

  Quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) catalyzes an unusual phosphoribosyl transfer that is linked to a decarboxylation reaction to form the NAD precursor nicotinate mononucleotide, carbon dioxide, and pyrophosphate from quinolinic acid (QA) and 5-phosphoribosyl I-pyrophosphate (PRPP). Structural studies and sequence similarities with other PRTases have implicated Glu214, Asp235, Lys153, and Lys284 in contributing to catalysis through direct interaction with PRPP. The four residues were substituted by site-directed mutagenesis. A nadC deletant form of BL21DE3 was created to eliminate trace contamination by chromosomal QAPRTase. The mutant enzymes were readily purified and retained their dimeric aggregation state oil gel filtration. Substitution of Lys153 with Ala resulted in an inactive enzyme, indicating its essential nature. Mutation of Glu214 to Ala or Asp caused at least a 4000-fold reduction in k(cat), with 10-fold increases in K-m and K-D values for PRPP. However, mutation of Glu214 to Gln had only modest effects on ligand binding and catalysis. pH profiles indicated that the deprotonated form of a residue with pK(a) of 6.9 is essential for catalysis, The WT-like pH profile of the E214Q Mutant indicated that Glu214 is not that residue. Mutation of Asp235 to Ala did not affect ligand binding or catalysis. Mutation of Lys284 to Ala decreased k(cat) by 30-fold and increased K-m and K-D values for PRPP by 80-fold and at least 20-fold, respectively. The Study Suggests that Lys153 is necessary for catalysis and important for PRPP binding, Glu214 provides a hydrogen bond necessary for catalysis but does not act as a base or electrostatically to stabilize the transition state, Lys284 is involved in PRPP binding, and Asp235 is not essential.

  DOI：

  10.1021/bi9018219

文献信息

• Bifunctional NadC Homologue PyrZ Catalyzes Nicotinic Acid Formation in Pyridomycin Biosynthesis
  作者：Zihua Zhou、Xu Yang、Tingting Huang、Jianting Zheng、Zixin Deng、Shaobo Dai、Shuangjun Lin

  DOI：10.1021/acschembio.2c00773

  日期：2023.1.20

  NadC homologue and catalyzes the successive formation, dephosphorylation, and ribose hydrolysis of nicotinic acid mononucleotide (NAMN) to generate nicotinic acid (NA), a biosynthetic precursor for the pyridyl moiety of pyridomycin. Crystal structures of PyrZ in complex with substrate quinolinic acid (QA) and the final product NA revealed a specific salt bridge formed between K184 and the C3-carboxyl

  Pyridomycin 是一种有效的抗分枝杆菌天然产物，通过特异性抑制 InhA，InhA 是一种临床验证的抗结核药物发现靶标。吡啶霉素的吡啶基部分通过占据烟酰胺腺嘌呤二核苷酸 (NADH) 辅助因子结合位点的还原形式，在抑制 InhA 中发挥重要作用。在此，我们对 PyrZ 进行生化表征，它是一种多功能 NadC 同系物，可催化烟酸单核苷酸 (NAMN) 的连续形成、去磷酸化和核糖水解，生成烟酸 (NA)，烟酸 (NA) 是吡啶霉素吡啶基部分的生物合成前体。与底物喹啉酸 (QA) 和最终产物 NA 复合的 PyrZ 的晶体结构揭示了在 K184 和 QA 的 C3-羧基之间形成的特定盐桥。这种相互作用将 QA 定位为接受磷酸核糖基团以生成 NAMN，将 NAMN 保留在活性位点内，并介导其易位至亲核试剂 D296 以进行去磷酸化。结合动力学和热力学分析与定点诱变，提出了 PyrZ 去磷酸
• AMINO ACID SALTS OF NICOTINIC ACID MONONUCLEOTIDE AND NICOTINAMIDE MONONUCLEOTIDE AS ANTI-AGEING AGENTS
  申请人：Jumpstart Fertility Pty Ltd

  公开号：EP3794011A1

  公开（公告）日：2021-03-24
• SELECTIVE SOLVENT FREE PHOSPHORYLATION
  申请人：ChromaDex, Inc.

  公开号：US20160355539A1

  公开（公告）日：2016-12-08

  A synthetic process is provided for the preparation of phosphorylated analogs of nicotinamide riboside (“NR”) having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II), wherein X − , Y 1 , Y 2 , Z 1 , Z 2 , n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined herein. The present disclosure also relates to the preparation of phosphorylated analogs of nicotinic acid riboside (“NAR”) having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II). Generally solvent-free conditions are employed using appropriate mechano-chemical techniques as described.
• 4,5-DIHYDROISOXAZOLE DERIVATIVES AS NAMPT INHIBITORS
  申请人：AURIGENE DISCOVERY TECHNOLOGIES LIMITED

  公开号：US20170204092A1

  公开（公告）日：2017-07-20

  The present invention provides 4,5-dihydroisoxazole derivatives of formula (I), which may be therapeutically useful, more particularly as NAMPT inhibitors. wherein, ring A, L 1 , L 2 , X 1 , X 2 , X 3 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , m, n, p and q have the meanings given in the specification and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder, caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPT) in a mammal. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted 4,5-di hydroisoxazole derivatives of formula (I) or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.
• AMINO ACID SALTS OF NICOTINIC ACID MONONUCLEOTIDE AND NICOTINAMIDE MONONUCLOETIDE AS ANTI-AGEING AGENTS
  申请人：Life Biosciences, Inc.

  公开号：US20210309685A1

  公开（公告）日：2021-10-07

  The present invention relates to amino acid salts of nicotinic acid mononucleotides and nicotinamide mononucleotides and compositions thereof of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD + : wherein A, M 1 , M 2 , R 1 , R 2 , and R 3 are as described herein.