uridine 5'-(7-deoxy-α-D-gluco-hept-6-ulopyranosyl diphosphate)

• 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: uridine 5'-(7-deoxy-α-D-gluco-hept-6-ulopyranosyl diphosphate)
• 英文别名: [(2R,3R,4S,5S,6S)-6-acetyl-3,4,5-trihydroxyoxan-2-yl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate
• 化学式: C₁₆H₂₄N₂O₁₇P₂
• 分子量: 578.317
• InChiKey: VVPMWAOLHSBQIM-BHRKRZAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.2
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  288
• 氢给体数：
  8
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  尿苷-5'-三磷酸 、 7-deoxy-D-gluco-hept-6-ulopyranosyl phosphate sodium salt 在 无机焦磷酸酶 、 UDP-glucose pyrophosphorylase 、 HEPES buffer 作用下， 以 水 为溶剂， 生成 uridine 5'-(7-deoxy-α-D-gluco-hept-6-ulopyranosyl diphosphate)
  参考文献：
  名称：

  UDP-Glucose Analogues as Inhibitors and Mechanistic Probes of UDP-Glucose Dehydrogenase

  摘要：

  UDP-glucose dehydrogenase catalyzes the NAD(+)-dependent 2-fold oxidation of UDP-glucose to give UDP-glucuronic acid. The putative aldehyde intermediate is not released from the active site and is presumably tightly bound. We have prepared UDP-7-deoxy-alpha-D-gluco-hept-6-ulopyranose 5, that contains a methyl ketone at C-6 and cannot be further oxidized by the enzyme. Ketone 5 was found to be a competitive inhibitor of the dehydrogenase from Streptococcus pyogenes with a K-I value of 6.7 mu M. We have also prepared the secondary alcohols UDP-6S-6C-methylglucose, 4a, and UDP-6R-6C-methylglucose, 4b. Compound 4a, but not 4b, was found to be a slow substrate for the dehydrogenase and was converted into the ketone inhibitor 5. This is consistent with the notion that the pro-R hydride is transferred in the first oxidation step of the normal enzymatic reaction.

  DOI：

  10.1021/jo991092h

文献信息

• UDP-Glucose Analogues as Inhibitors and Mechanistic Probes of UDP-Glucose Dehydrogenase
  作者：Robert E. Campbell、Martin E. Tanner

  DOI：10.1021/jo991092h

  日期：1999.12.1

  UDP-glucose dehydrogenase catalyzes the NAD(+)-dependent 2-fold oxidation of UDP-glucose to give UDP-glucuronic acid. The putative aldehyde intermediate is not released from the active site and is presumably tightly bound. We have prepared UDP-7-deoxy-alpha-D-gluco-hept-6-ulopyranose 5, that contains a methyl ketone at C-6 and cannot be further oxidized by the enzyme. Ketone 5 was found to be a competitive inhibitor of the dehydrogenase from Streptococcus pyogenes with a K-I value of 6.7 mu M. We have also prepared the secondary alcohols UDP-6S-6C-methylglucose, 4a, and UDP-6R-6C-methylglucose, 4b. Compound 4a, but not 4b, was found to be a slow substrate for the dehydrogenase and was converted into the ketone inhibitor 5. This is consistent with the notion that the pro-R hydride is transferred in the first oxidation step of the normal enzymatic reaction.