[4-2H]-NAD(1+) | 60797-91-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: [4-2H]-NAD(1+)
• 英文别名: [4-²H]NAD⁺；diphosphoric acid-1-adenosin-5'-ylester-2-[(1R)-1-(3-carbamoyl-4-deuterio-pyridinio)-D-1,4-anhydro-ribitol-5-ylester]-betaine；Diphosphorsaeure-1-adenosin-5'-ylester-2-[(1R)-1-(3-carbamoyl-4-deuterio-pyridinio)-D-1,4-anhydro-ribit-5-ylester]-betain；[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoyl-4-deuteriopyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• CAS: 60797-91-3
• 化学式: C₂₁H₂₇N₇O₁₄P₂
• 分子量: 664.423
• InChiKey: BAWFJGJZGIEFAR-DLZGGDIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  321
• 氢给体数：
  7
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  [4-2H]-NAD(1+) 在 水 、 氢气 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 [4R-2H]-NADH
  参考文献：
  名称：

  Synthesis of [4 S ‐ ² H]NADH, [4 R ‐ ² H]NADH, [4‐ ² H ₂ ]NADH and [4‐ ² H]NAD ⁺ cofactors through heterogeneous biocatalysis in heavy water

  摘要：

  该操作协议描述了一系列重氢化的烟酰胺辅酶的合成： [4S-2H]NADH、[4R-2H]NADH、[4-2H2]NADH和[4-2H]NAD+。应用最近开发的H2驱动异相生物催化剂，使辅酶能够以超过90%的高重氢掺入率合成，仅使用2H2O作为同位素来源。

  DOI：

  10.1002/jlcr.3899
• 作为产物：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 氢气 、 重水 、 苯乙酮 、 alcohol dehydrogenase 作用下， 以 aq. buffer 为溶剂， 反应 136.0h， 生成 [4-2H]-NAD(1+)
  参考文献：
  名称：

  Synthesis of [4 S ‐ ² H]NADH, [4 R ‐ ² H]NADH, [4‐ ² H ₂ ]NADH and [4‐ ² H]NAD ⁺ cofactors through heterogeneous biocatalysis in heavy water

  摘要：

  该操作协议描述了一系列重氢化的烟酰胺辅酶的合成： [4S-2H]NADH、[4R-2H]NADH、[4-2H2]NADH和[4-2H]NAD+。应用最近开发的H2驱动异相生物催化剂，使辅酶能够以超过90%的高重氢掺入率合成，仅使用2H2O作为同位素来源。

  DOI：

  10.1002/jlcr.3899

文献信息

• Stereochemistry of reduction of the endocyclic double bond of (−)-carvone with the enzyme preparation from cultured cells of Nicotiana tabacum
  作者：Toshifumi Hirata、Yixiong Tang、Kuniko Okano、Takayuki Suga

  DOI：10.1016/0031-9422(89)80341-3

  日期：——

  endocyclic double bond; (ii) the reduction occurs stereospecifically by anti addition of hydrogen from the si face at C-1 and the re face at C-6 of carvone, resulting in the formation of (1 R , 4 R )-(+)-dihydrocarvone; (iii) the hydrogen atoms participating in the enzymatic reduction at C-1 and C-6 originate from the medium and the pro -4 R hydrogen of NADH, respectively.

  摘要 通过2 H NMR和质谱研究了用来自烟草培养细胞的酶制剂还原(4 R )-(-)-香芹酮的环内CC​​双键的立体化学。发现：(i)酶制剂仅区域选择性地还原环内双键；(ii) 通过从香芹酮的 C-1 处和 C-6 处的反加氢反加成氢而立体定向地发生还原，导致形成 (1 R , 4 R )-(+)-二氢香芹酮；(iii) 参与 C-1 和 C-6 酶促还原的氢原子分别来自介质和 NADH 的 pro -4 R 氢。
• Measurement of the Kinetic Isotope Effect for the Oxidation of NADH at a Poly(aniline)-Modified Electrode
  作者：Philip N. Bartlett、Evelyne Simon

  DOI：10.1021/ja028943e

  日期：2003.4.1

  measurements using [4,4-2H2]NADH and [4-1H, 4-2H]NADH have been used to investigate the mechanism of the electrochemical oxidation of NADH at poly(aniline)-poly(vinyl sulfonate)-modified electrodes. The experiments show a primary kinetic isotope effect for the reaction of 4.2. This is consistent with literature values for the corresponding isotope effect for the oxidation of NADH by two-electron oxidants

  使用 [4,4-2H2]NADH 和 [4-1H, 4-2H]NADH 的动力学同位素测量已被用于研究 NADH 在聚（苯胺）-聚（乙烯基磺酸盐）修饰电极上电化学氧化的机制. 实验显示了 4.2 反应的主要动力学同位素效应。这与在均相溶液中双电子氧化剂氧化 NADH 的相应同位素效应的文献值一致。结果表明，H 从 NADH 转移到修饰电极发生在反应复合物中的限速步骤中。
• Secoisolariciresinol dehydrogenase: mode of catalysis and stereospecificity of hydride transfer in Podophyllum peltatum
  作者：Syed G. A. Moinuddin、Buhyun Youn、Diana L. Bedgar、Michael A. Costa、Gregory L. Helms、ChulHee Kang、Laurence B. Davin、Norman G. Lewis

  DOI：10.1039/b516563f

  日期：——

  Secoisolariciresinol dehydrogenase (SDH) catalyzes the NAD+ dependent enantiospecific conversion of secoisolariciresinol into matairesinol. In Podophyllum species, (−)-matairesinol is metabolized into the antiviral compound, podophyllotoxin, which can be semi-synthetically converted into the anticancer agents, etoposide, teniposide and Etopophos®. Matairesinol is also a precursor of the cancer-preventative “mammalian” lignan, enterolactone, formed in the gut following ingestion of, for example, various high fiber dietary foods, as well as being an intermediate to numerous defense compounds in vascular plants. This study investigated the mode of enantiospecific Podophyllum SDH catalysis, the order of binding, and the stereospecificity of hydride abstraction/transfer from secoisolariciresinol to NAD+. SDH contains a highly conserved catalytic triad (Ser153, Tyr167 and Lys171), whose activity was abolished with site-directed mutagenesis of Tyr167Ala and Lys171Ala, whereas mutagenesis of Ser153Ala only resulted in a much reduced catalytic activity. Isothermal titration calorimetry measurements indicated that NAD+ binds first followed by the substrate, (−)-secoisolariciresinol. Additionally, for hydride transfer, the incoming hydride abstracted from the substrate takes up the pro-S position in the NADH formed. Taken together, a catalytic mechanism for the overall enantiospecific conversion of (−)-secoisolariciresinol into (−)-matairesinol is proposed.

  塞克异橄榄醇脱氢酶（SDH）催化依赖于NAD+的enantiospecific反应，将塞克异橄榄醇转化为马台醇。在马兜铃属植物中，(−)-马台醇被代谢为抗病毒化合物——马兜铃毒素，该化合物可以半合成转化为抗癌药物异尾酰胺、替尼酰胺和Etopophos®。马台醇还是癌症预防性“哺乳动物”木酚类化合物——肠内乳酸的前体，后者在摄入例如各种高纤维饮食食品后在肠道中形成。此外，马台醇还是维管植物中众多防御化合物的中间产物。本研究调查了马兜铃属SDH催化的enantiospecific模式、结合顺序及从塞克异橄榄醇到NAD+的氢化物抽取/转移的立体特异性。SDH包含一个高度保守的催化三联体（Ser153、Tyr167和Lys171），其中Tyr167Ala和Lys171Ala的定点突变会使活性丧失，而Ser153Ala的突变仅导致催化活性显著降低。等温滴定量热法测量表明，NAD+首次结合，然后是底物(−)-塞克异橄榄醇。此外，对于氢化物转移，底物中引入的氢化物在形成的NADH中占据pro-S位。综合来看，提出了(−)-塞克异橄榄醇向(−)-马台醇的整体enantiospecific转化的催化机制。
• Stereochemistry in the reduction of enones by the reductase from euglena gracilis z
  作者：Kei Shimoda、Toshifumi Hirata、Yoshiaki Noma

  DOI：10.1016/s0031-9422(97)00858-3

  日期：1998.9

  A reductase, which catalyses the NADH-dependent reduction of the C=C bond adjacent to the carbonyl group, was characterized with regard to the stereochemistry of the hydrogen transfer into the substrate. The reductase was isolated from Euglena gracilis Z and was found to reduce stereospecifically the C=C bond of carvone by anti-addition of hydrogen from the si face at a-position to the carbonyl group and the re face at beta-position. The hydrogen atoms participating in the enzymatic reduction at alpha- and beta-position to the carbonyl group originate from the medium and the pro-4R hydrogen of NADH, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Chemical formation of 4-hydroxy-2,5-dimethyl-3[2H]-furanone from d-fructose 1,6-diphosphate
  作者：Tobias Hauck、Christian Landmann、Thomas Raab、Fredi Brühlmann、Wilfried Schwab

  DOI：10.1016/s0008-6215(02)00121-0

  日期：2002.7

  The selective chemical formation of 4-hydroxy-2,5-dimethyl-3[2H]-furanone (HDF) from D-fructose 1,6-diphosphate in the presence of reduced nicotinamide-adenine-dinucleotides (NAD(P)H) was investigated by means of HPLC-DAD and HPLC-UV-MS/MS. The temperature optimum for HDF formation was 30 degreesC, whereas the pH value (pH 3-10) and chemical nature of the buffer had no significant influence. A linear correlation of reaction time and D-fructose 1,6-diphosphate concentration with the obtained HDF yield was observed. Proteins appeared to have a stabilizing effect. The NAD(P)H were mandatory, even in the presence of protein, implying a non-enzymatic hydride-transfer to an unknown intermediate which finally leads to the selective formation of HDF. The hydride-transfer was confirmed by the application of selectively pro-4R or pro-4S deuterium labeled NADH resulting in each case in the formation of HDF exhibiting a deuterium labeling of approx 30% and employment of [4R,S-H-2(2)]-NADH led to a deuterium labeling of approx 66%. The incubation of [1-C-13]-D-fructose 1,6-diphosphate with [4R,S-H-2(2)]-NADH revealed that the hydride is transferred to C-5 or C-6 of the D-fructose 1,6-diphosphate skeleton. Thus, a chemical HDF formation from D-fructose 1,6-diphosphate under physiological reaction conditions was shown and for the first time to our knowledge a non-enzymatic hydride-transfer from NADH to a carbohydrate structure was demonstrated. (C) 2002 Elsevier Science Ltd. All rights reserved.