guanosine dioxolane triphosphate

• 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: guanosine dioxolane triphosphate
• 英文别名: DXG-TP；[[(2R,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)-1,3-dioxolan-2-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate；[[(2R,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)-1,3-dioxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• 化学式: C₉H₁₄N₅O₁₃P₃
• 分子量: 493.157
• InChiKey: VZRURNYATGBLIL-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  264
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  在 human nucleoside diphosphate kinase (form A) 、 sodium fluoride 、 5’-三磷酸腺苷 作用下， 以 various solvents 为溶剂， 生成 guanosine dioxolane triphosphate
  参考文献：
  名称：

  Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5′-phosphates by mammalian phosphotransferases

  摘要：

  Amdoxovir [(-)-beta-D-2,6-diaminopurine dioxolane, DAPD], the prodrug of dioxolane guanosine (DXG), is currently in Phase I/II clinical development for the treatment of HIV-1 infection. In this study, we examined the phosphorylation pathway of DXG using 15 purified enzymes from human (8), animal (6), and yeast (1) sources, including deoxyguanosine kinase (dGK), deoxycytidine kinase ;dCK), high K-m 5'-nucleotidase (5'-NT), guanylate (GMP) kinase, nucleoside monophosphate (NMP) kinase, adenylate (AMP) kinase, nucleoside diphosphate (NDP) kinase, 3-phosphoglycerate (3-PG) kinase, creatine kinase, and pyruvate kinase. In addition, the metabolism of C-14-labeled DXG was studied in CEM cells. DXG was not phosphorylated by human dCK, and was a poor substrate for human dGK with a high K-m (7 mM). Human 5'-NT phosphorylated DXG with relatively high efficiency (4.2% of deoxyguanosine). DXG-MP was a substrate for porcine brain GMP kinase with a substrate specificity that was 1% of dGMP. DXG-DP was phosphorylated by all of the enzymes tested, including NDP kinase, 3-PG kinase, creatine kinase, and pyruvate kinase. The BB-isoform of human creatine kinase showed the highest relative substrate specificity (47% of dGDP) for DXG-DP. In CEM cells incubated with 5 muM DXG for 24 h, 0.015 pmole/10(6) cells (similar to7.5 nM) of DXG-TP was detected as the primary metabolite. Our study demonstrated that 5'-nucleotidase, GMP kinase, creatine kinase, and NDP kinase could be responsible for the activation of DXG in vivo. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2004.06.019