8-Br-NAD+ | 52977-37-4

• 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: 8-Br-NAD+
• 英文别名: [[(2R,3S,4R,5R)-5-(6-amino-8-bromopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• CAS: 52977-37-4
• 化学式: C₂₁H₂₆BrN₇O₁₄P₂
• 分子量: 742.327
• InChiKey: ISNAGOUAZGHQIY-NAJQWHGHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  45
• 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：

  8-Br-NAD+ 在 baker's yeast alcohol dehydrogenase 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 生成 [[(2R,3S,4R,5R)-5-[6-amino-8-(6-aminohexylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
  参考文献：
  名称：

  Kinetics and docking studies on the effect of chemical modification of NADH for redox reactions with dehydrogenases

  摘要：

  Cofactor analogs promise important applications in biosynthesis. The effect of chemical modification on the reactivity of NADH for redox reactions catalyzed by dehydrogenases was examined in this work. Compared with the native NADH, kinetics and molecular docking studies with 8-(6-aminohexyl)-amino-NADH showed that its binding with alcohol dehydrogenase (ADH) was not much affected or even enhanced by a factor of 4.9-fold with lactate dehydrogenase (LDH), but complicated the binding of substrates to the enzymes. For ADH, the Michaelis constant for acetaldehyde decreased from 0.47 to 0.048 mM, while that of sodium pyruvate with LDH increased to 0.81 from 0.18 mM. On the other hand, the modified coenzyme showed a 19.3-fold decrease in turnover number (k(cat)) with ADH, while a slight increase with LDH. Molecular docking analysis showed that the hexanediamine arm on the modified coenzyme generated an extra hydrogen bond at the active site of ADH, as well as additional hydrophobic interactions with both ADH and LDH. It appeared that the apparently decreased reactivity of modified cofactor with ADH was caused mainly by the enhanced stability of ternary coenzyme-enzyme-substrate complex, while in the case of LDH, the reduced substrate binding as a result of the chemical modification of NADH led to a slight increase in the overall reaction reactivity. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2012.01.018
• 作为产物：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 acetate buffer 、 溴 作用下， 以 水 为溶剂， 反应 1.0h， 生成 8-Br-NAD+
  参考文献：
  名称：

  氟化NAD作为可溶辅酶的合成，用于在含氟溶剂和二氧化碳中进行酶促化学反应

  摘要：

  报道了具有共价连接的氟化聚合物的辅酶烟酰胺腺嘌呤二核苷酸（NAD）的合成。由于全氟聚醚的附着，使得氟化NAD（FNAD）可溶于氟溶剂和液态二氧化碳中。马肝醇脱氢酶（HLADH）在含氟溶剂，甲氧基九氟丁烷（HFE）和液态二氧化碳中使用FNAD作为可溶性辅酶的催化氧化/还原反应中具有活性。在两种溶剂中，使用FNAD的HLADH的活性均大于相同摩尔量的未修饰（不溶）NAD，表明可溶性辅酶可导致更有效的反应。

  DOI：

  10.1016/s0040-4020(02)00259-4

文献信息

• Synthesis of conjugates of 11α-hydroxyprogesterone with β-nicotinamide adenine dinucleotide (β-NAD) and adenosine triphosphate (ATP)
  作者：David N. Kirk、Barry W. Miller

  DOI：10.1039/p19880002983

  日期：——

  Conjugates of 11α-hydroxyprogesterone with adenosine triphosphate and nicotinamide adenine dinucleotide have been prepared in which the steroid is attached to the nucleotides via bridges from C-11 to the terminal phosphate and C-8 positions of ATP, and to the N-6 and C-8 positions on the adenine ring of NAD. Preliminary evaluation of the bioluminescence of these conjugates is reported.

  已经制备了11α-羟基孕酮与三磷酸腺苷和烟酰胺腺嘌呤二核苷酸的结合物，其中类固醇通过从C-11到ATP的末端磷酸和C-8位置以及N-6和C的桥连接到核苷酸上。 NAD腺嘌呤环上的-8位。报道了对这些缀合物的生物发光的初步评估。
• 2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives
  作者：Bo Zhang、Gerd K. Wagner、Karin Weber、Clive Garnham、Anthony J. Morgan、Antony Galione、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm7010386

  日期：2008.3.1

  The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2'-deoxy-cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8-O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5'-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2'-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2'-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2'-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membrane-permeant in whole eggs. Classical antagonists 2 and 3 also showed. previously unobserved agonist activity at higher concentrations in both systems. The 2'-OH group, without effect on the Ca(2+)-mobilizing ability of cADPR itself, is an important motif for the antagonistic activities of 8-substituted cADPR analogues.
• KIRK, DAVID N.;MILLER, BARRY W., J. CHEM. SOC. PERKIN TRANS. PT 1,(1988) N1, C. 2983-2992
  作者：KIRK, DAVID N.、MILLER, BARRY W.

  DOI：——

  日期：——
• Synthesis of fluorinated NAD as a soluble coenzyme for enzymatic chemistry in fluorous solvents and carbon dioxide
  作者：Janice L Panza、Alan J Russell、Eric J Beckman

  DOI：10.1016/s0040-4020(02)00259-4

  日期：2002.5

  reported. The fluorinated NAD (FNAD) was rendered soluble in both fluorous solvents and liquid carbon dioxide due to the attachment of a perfluoropolyether. The enzyme horse liver alcohol dehydrogenase (HLADH) was active in catalyzing oxidation/reduction reactions using FNAD as a soluble coenzyme in a fluorous solvent, methoxynonafluorobutane (HFE), and liquid carbon dioxide. In both solvents, the activity

  报道了具有共价连接的氟化聚合物的辅酶烟酰胺腺嘌呤二核苷酸（NAD）的合成。由于全氟聚醚的附着，使得氟化NAD（FNAD）可溶于氟溶剂和液态二氧化碳中。马肝醇脱氢酶（HLADH）在含氟溶剂，甲氧基九氟丁烷（HFE）和液态二氧化碳中使用FNAD作为可溶性辅酶的催化氧化/还原反应中具有活性。在两种溶剂中，使用FNAD的HLADH的活性均大于相同摩尔量的未修饰（不溶）NAD，表明可溶性辅酶可导致更有效的反应。
• Kinetics and docking studies on the effect of chemical modification of NADH for redox reactions with dehydrogenases
  作者：Hongjing Ma、Songping Zhang、Zhiguo Su、Ping Wang

  DOI：10.1016/j.molcatb.2012.01.018

  日期：2012.5

  Cofactor analogs promise important applications in biosynthesis. The effect of chemical modification on the reactivity of NADH for redox reactions catalyzed by dehydrogenases was examined in this work. Compared with the native NADH, kinetics and molecular docking studies with 8-(6-aminohexyl)-amino-NADH showed that its binding with alcohol dehydrogenase (ADH) was not much affected or even enhanced by a factor of 4.9-fold with lactate dehydrogenase (LDH), but complicated the binding of substrates to the enzymes. For ADH, the Michaelis constant for acetaldehyde decreased from 0.47 to 0.048 mM, while that of sodium pyruvate with LDH increased to 0.81 from 0.18 mM. On the other hand, the modified coenzyme showed a 19.3-fold decrease in turnover number (k(cat)) with ADH, while a slight increase with LDH. Molecular docking analysis showed that the hexanediamine arm on the modified coenzyme generated an extra hydrogen bond at the active site of ADH, as well as additional hydrophobic interactions with both ADH and LDH. It appeared that the apparently decreased reactivity of modified cofactor with ADH was caused mainly by the enhanced stability of ternary coenzyme-enzyme-substrate complex, while in the case of LDH, the reduced substrate binding as a result of the chemical modification of NADH led to a slight increase in the overall reaction reactivity. (C) 2012 Elsevier B.V. All rights reserved.