<1'-14C>-adenosine | 103960-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: <1'-14C>-adenosine
• 英文别名: [1'-14C]-adenosine；(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)(214C)oxolane-3,4-diol
• CAS: 103960-06-1
• 化学式: C₁₀H₁₃N₅O₄
• 分子量: 269.233
• InChiKey: OIRDTQYFTABQOQ-RTCWRAIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [1'-(14)C]ATP 在 alkaline phosphatase adenylate kinase 、 葡萄糖 、 hexokinase 作用下， 生成 <1'-14C>-adenosine
  参考文献：
  名称：

  Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

  摘要：

  Adenosine deaminases (ADAs) from human, bovine, and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in B- and T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph, and its inhibition is expected to have therapeutic effects for malaria. Therefore, ADA is of continuing interest for inhibitor design. Stable structural mimics of ADA transition states are powerful inhibitors. Here we report the transition-state structures of PfADA, HsADA, and bovine ADA (BtADA) solved using competitive kinetic isotope effects (KIE) and density functional calculations. Adenines labeled at [6-C-13], [6-N-15], [6-C-13, 6-N-15], and [1-N-15] were synthesized and enzymatically coupled with [1'-C-14] ribose to give isotopically labeled adenosines as ADA substrates for KIE analysis. [6-C-13], [6-N-15], and [1-N-15]adenosines reported intrinsic KIE values of (1.010, 1.011, 1.009), (1.005, 1.005, 1.002), and (1.004, 1.001, 0.995) for PfADA, HsADA, and BtADA, respectively. The differences in intrinsic KIEs reflect structural alterations in the transition states. The [1-N-15] KIEs and computational modeling results indicate that PfADA, HsADA, and BtADA adopt early SNAr transition states, where N1 protonation is partial and the bond order to the attacking hydroxyl nucleophile is nearly complete. The key structural variation among PfADA, HsADA, and BtADA transition states lies in the degree of N1 protonation with the decreased bond lengths of 1.92, 1.55, and 1.28 angstrom, respectively. Thus, PfADA has the earliest and BtADA has the most developed transition state. This conclusion is consistent with the 20-36-fold increase of k(cat) in comparing PfADA with HsADA and BtADA.

  DOI：

  10.1021/ja072122y

文献信息

• The biosynthesis of sinefungin: Investigations using a cell-free system
  作者：Ronald J. Parry、Shyhchen Ju

  DOI：10.1016/s0040-4020(01)86497-8

  日期：1991.7

  The origin of the adenylyl moiety of sinefungin has been investigated by administration of doubly-labeled forms of ATP and adenosine to cell-free extracts of Streptomyces griseolus. The results demonstrated that both ATP and adenosine are significantly degraded by the extract before incorporation into sinefungin. However, the ribose ring of adenosine was shown to be incorporated into sinefungin intact

  西奈芬净的腺苷基部分的起源已经通过向灰链链霉菌的无细胞提取物施用双标记形式的ATP和腺苷进行了研究。结果表明，在掺入西芬芬净之前，提取物会显着降解ATP和腺苷。然而，显示腺苷的核糖环完整地并入西芬芬净中，并且不会从C-5'中损失tri。该观察结果排除了A9145C在西芬芬净生物合成中的中介作用。描述了另外的实验，这些实验表明精氨酸的C-5和核糖衍生物的C-5之间的CC键形成可以在腺嘌呤环的连接之前。