β-L-2'-deoxyuridine 5'-monophosphate | 96744-87-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: β-L-2'-deoxyuridine 5'-monophosphate
• 英文别名: L-dUMP；deoxyuridine monophosphate；dUMP；1-(2-deoxy-5-O-phosphono-beta-L-erythro-pentofuranosyl)pyrimidine-2,4(1H,3H)-dione；[(2S,3R,5S)-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 96744-87-5
• 化学式: C₉H₁₃N₂O₈P
• 分子量: 308.185
• InChiKey: JSRLJPSBLDHEIO-CHKWXVPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  146
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 reduced flavin-dependent thymidylate synthase from Thermatoga maritima 、 水 作用下， 以 aq. buffer 为溶剂， 反应 1.0h， 生成 β-L-2'-deoxyuridine 5'-monophosphate
  参考文献：
  名称：

  Substrate Activation in Flavin-Dependent Thymidylate Synthase

  摘要：

  Thymidylate is a critical DNA nucleotide that has to be synthesized in cells de novo by all organisms. Flavin-dependent thymidylate synthase (FDTS) catalyzes the final step in this de novo production of thymidylate in many human pathogens, but it is absent from humans. The FDTS reaction proceeds via a chemical route that is different from its human enzyme analogue, making FDTS a potential antimicrobial target. The chemical mechanism of FDTS is still not understood, and the two most recently proposed mechanisms involve reaction intermediates that are unusual in pyrimidine biosynthesis and biology in general. These mechanisms differ in the relative timing of the reaction of the flavin with the substrate. The consequence of this difference is significant: the intermediates are cationic in one case and neutral in the other, an important consideration in the construction of mechanism-based enzyme inhibitors. Here we test these mechanisms via chemical trapping of reaction intermediates, stopped-flow, and substrate hydrogen isotope exchange techniques. Our findings suggest that an initial activation of the pyrimidine substrate by reduced Flavin is required for catalysis, and a revised mechanism is proposed on the basis of previous and new data. These findings and the newly proposed mechanism add an important piece to the puzzle of the mechanism of FDTS and suggest a new class of intermediates that, in the future, may serve as targets for mechanism-based design of FDTS-specific inhibitors.

  DOI：

  10.1021/ja506108b

文献信息

• Enantio-Selectivity of Human Nucleoside Monophosphate Kinases
  作者：J. A. C. Alexandre、B. Roy、D. Topalis、C. Périgaud、D. Deville-Bonne

  DOI：10.1080/15257770701534014

  日期：2007.11.26

  activity of these compounds requires phosphorylation to their triphosphate form, involving nucleoside monophosphate kinases in the second step. In order to characterize the activation pathway of l-nucleosides of the pyrimidine series, we studied the enantio-selectivity of human uridylate-cytidylate and thymidylate kinases. The results showed that these enzymes are only weakly enantio-selective and are thus

  近年来，人们对开发作为治疗病毒感染的安全有效药物的l-核苷产生了新的兴趣。这些化合物的生物活性需要磷酸化为三磷酸形式，第二步涉及核苷单磷酸激酶。为了表征嘧啶系列的I-核苷的激活途径，我们研究了人尿苷酸-胞苷酸和胸苷酸激酶的对映选择性。结果表明，这些酶仅具有弱对映体选择性，因此可能在体内参与了1-核苷的活化。因此提出了替比夫定（1-dT）的激活途径。