[6-14C]D-glucose | 771-89-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [6-14C]D-glucose
• 英文别名: <6-14C>glucose；D-[6-¹⁴C]glucose；[6-¹⁴C]D-glucose；D-[6-(14)C]glucose；D-[6-¹⁴C]glucose；6-(14)C-glucose；6-14>-D-glucose
• CAS: 771-89-1
• 化学式: C₆H₁₂O₆
• 分子量: 182.147
• InChiKey: WQZGKKKJIJFFOK-MZLOEJLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.22
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  110.38
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [6-14C]D-glucose 、 腺嘌呤 在 glucose-6-phosphate dehydrogenase 、 pyruvate kinase 、 双甘肽 、 磷烯醇丙酮酸 、 adenine phosphoribosyltransferase 、 decaprenyl-phosphate phosphoribosyltransferase 、 5’-三磷酸腺苷 、 potassium hydroxide 、 magnesium chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 反应 20.0h， 生成 ((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl-14C tetrahydrogen triphosphate
  参考文献：
  名称：

  人胸苷磷酸化酶对胸苷水解的过渡态分析

  摘要：

  人胸苷磷酸化酶 (hTP) 负责胸苷 (dT) 稳态，其作用促进血管生成。在没有磷酸盐的情况下，hTP 催化 dT 的缓慢水解脱嘧啶，产生胸腺嘧啶和 2-脱氧核糖 (dRib)。其过渡态使用多重动力学同位素效应 (KIE) 测量进行表征。富含同位素的胸苷由葡萄糖或（脱氧）核糖酶促合成，内在 KIE 用于解释过渡态结构。来自 [1'-(14)C]-、[1-(15)N]-、[1'-(3)H]-、[2'R-(3)H]-、[2'S-( 3)H]-、[4'-(3)H]- 和 [5'-(3)H]dTs 提供的值为 1.033 ± 0.002、1.004 ± 0.002、1.325 ± 0.003、1.101 ± 0.004、± 1.085 、 1.040 ± 0.003 和 1.033 ± 0.003。过渡态分析揭示了一种逐步机制，即早期形成的 2-脱氧核糖化以及水分子对高能中间体的亲核攻击的更高能量

  DOI：

  10.1021/ja105041j

文献信息

• Recycling Nicotinamide. The Transition-State Structure of Human Nicotinamide Phosphoribosyltransferase
  作者：Emmanuel S. Burgos、Mathew J. Vetticatt、Vern L. Schramm

  DOI：10.1021/ja310180c

  日期：2013.3.6

  determined the TS structure for pyrophosphorolysis of nicotinamide mononucleotide (NMN) from kinetic isotope effects (KIEs). With the natural substrates, NMN and pyrophosphate (PPi), the intrinsic KIEs of [1'-(14)C], [1-(15)N], [1'-(3)H], and [2'-(3)H] are 1.047, 1.029, 1.154, and 1.093, respectively. A unique quantum computational approach was used for TS analysis that included structural elements of the catalytic

  人烟酰胺磷酸核糖转移酶 (NAMPT) 补充 NAD 库并控制去乙酰化酶、单和聚 (ADP-核糖) 聚合酶以及 NAD 核苷酶的活性。酶过渡态 (TS) 的性质对于理解 NAMPT 的功能至关重要。我们通过动力学同位素效应 (KIE) 确定了烟酰胺单核苷酸 (NMN) 焦磷酸解的 TS 结构。使用天然底物 NMN 和焦磷酸盐 (PPi)，内在 KIE 为 [1'-(14)C]、[1-(15)N]、[1'-(3)H] 和 [2'- (3)H]分别为1.047、1.029、1.154和1.093。使用独特的量子计算方法进行 TS 分析，其中包括催化位点的结构元素。在没有约束（例如施加扭转角）的情况下，理论数据和实验数据非常一致。量子力学计算纳入了一个关键的催化位点残基（D313）、两个镁原子和配位水分子。 TS 模型预测初级 (14)C、α-次级 (3)H、β-次级 (3)H 和初级 (15)N
• Transition state structure of orotate phosphoribosyl transferases and uses thereof
  申请人：Schramm Vern L.

  公开号：US20110301104A1

  公开（公告）日：2011-12-08

  Methods are provided for designing a transition state inhibitor of orotate phosphoribosyltransferase (OPRT) and for inhibiting OPRT.

  提供了设计尿嘧啶磷酸核糖基转移酶（OPRT）过渡态抑制剂和抑制OPRT的方法。
• The Transition-State Structure for Human MAT2A from Isotope Effects
  作者：Ross S. Firestone、Vern L. Schramm

  DOI：10.1021/jacs.7b05803

  日期：2017.10.4

  inhibitors. We used kinetic isotope effect (KIE), commitment factor (Cf), and binding isotope effect (BIE) measurements combined with quantum mechanical (QM) calculations to solve the transition state structure of human MAT2A. The reaction is characterized by an advanced SN2 transition state. The bond forming from the nucleophilic methionine sulfur to the 5′-C of ATP is 2.03 Å at the transition state (bond

  人甲硫氨酸S-腺苷基转移酶（MAT2A）催化由ATP和甲硫氨酸形成S-腺苷甲硫氨酸（SAM）。合成致死遗传分析已将MAT2A作为缺乏5'-甲基硫代腺苷磷酸化酶（MTAP）表达的肿瘤细胞的抗癌靶标。大约15％的人类癌症是MTAP – / –。其余的可以呈现MTAP -通过MTAP抑制剂。我们将动力学同位素效应（KIE），承诺因子（C f）和结合同位素效应（BIE）测量与量子力学（QM）计算结合使用，以解决人类MAT2A的过渡态结构。该反应的特征在于先进的S N2过渡状态。从亲核蛋氨酸硫到ATP的5'-C形成的键在过渡态（键序为0.67）为2.03Å。ATP的离去基团三磷酸的离解进展顺利，并在ATP的5'-C与三磷酸的氧之间形成2.32Å键（键序为0.23）。MAT2A及其MAT2B调节亚基的相互作用不会导致内在KIE发生变化，表明相同的过渡态结构。与来自大肠杆菌的蛋氨酸腺苷基转移酶的近对称过
• Enzymic Synthesis of NAD+ with the Specific Incorporation of Atomic Labels
  作者：Kathleen A. Rising、Vern L. Schramm

  DOI：10.1021/ja00094a006

  日期：1994.7

  An enzymatic synthesis is described for the production of NAD(+) labeled with a radioactive or stable isotope at any desired position in the AMP or NMN(+) portions of the molecule. In the first step, ten enzyme-catalyzed reactions are coupled for the synthesis of nicotinic acid adenine dinucleotide (NaAD(+)) from glucose, nicotinic acid, and ATP. NAD(+) is formed from NaAD(+) and glutamine in the second step. Oxidized nicotinamide adenine dinucleotide was synthesized with H-3, C-14, or N-15 label specifically incorporated in the ribose or nicotinamide of the NMN(+) portion of NAD(+) as [H(N)1'H-3]NAD(+), [H(N)2'-H-3]NAD(+), [H(N)4'-H-3]NAD(+), [H(N)5'-H-3]NAD(+), [C(N)1'-C-14]NAD(+), [C(N)5'-C-14]NAD(+), [N(N)1-N-15, C(N)1'-C-14]NAD(+), and [N(N)1-N-15, C(N)5'-C-14]NAD(+). Nuclear magnetic resonance spectroscopy of [H(N)2'-H-2]NAD(+) as well as enzymatic degradation were used to verify the position of labels. Appropriately labeled glucose, ribose 5-phosphate, or nicotinic acid were the starting materials and were converted to NAD(+) using enzymes from the pentose pathway and the pathway for NAD(+) de novo synthesis. Yields of purified NAD(+) to 96% were obtained from starting glucose. The labeled NAD(+) is catalytically competent and is chromatographically and spectrophotometrically indistinguishable from authentic NAD(+). By using specifically labeled ATP as a precursor (Parkin, D. W.; Schramm, V. L. Biochemistry 1987, 26, 913-920), the method is readily adaptable for the synthesis of NAD(+) with single or multiple atomic labels at various positions in the AMP portion of the molecule. NAD(+) was synthesized from [8-C-14]ATP to give [C(A)8-C-14]NAD(+) as an example. Together these methods provide a general scheme for the efficient synthesis of NAD(+) of high purity with H-3, C-14, Or Other labels at any nonexchangeable position of the NMN(+) or AMP portions of the NAD(+) molecule.
• Zhang, Yong; Luo, Minkui; Schramm, Vern L., Journal of the American Chemical Society, 2009, vol. 131, p. 4685 - 4694
  作者：Zhang, Yong、Luo, Minkui、Schramm, Vern L.

  DOI：——

  日期：——