2'-deoxyguanosine-3',5'-di(methylene bisphosphonate) | 1187644-84-3

• 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: 2'-deoxyguanosine-3',5'-di(methylene bisphosphonate)
• 英文别名: [[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[hydroxy(phosphonomethyl)phosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]methylphosphonic acid
• CAS: 1187644-84-3
• 化学式: C₁₂H₂₁N₅O₁₄P₄
• 分子量: 583.219
• InChiKey: FBKHAJAKIHOGTN-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  303
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  亚甲基双膦酰二氯 、 2'-脱氧鸟苷 在 水 、 ammonium bicarbonate 作用下， 以 磷酸三甲酯 为溶剂， 反应 0.25h， 以73%的产率得到2'-deoxyguanosine-3',5'-di(methylene bisphosphonate)
  参考文献：
  名称：

  ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria

  摘要：

  A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5'-triphosphate-3'-diphosphate, and ppGpp: 5'-3'-bis-diphosphate), collectively called (p) ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p) ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p) ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2'-Deoxyguanosine-3'-5'-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site.As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.064

文献信息

• ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria
  作者：Ezequiel Wexselblatt、Jehoshua Katzhendler、Raspudin Saleem-Batcha、Guido Hansen、Rolf Hilgenfeld、Gad Glaser、Roee R. Vidavski

  DOI：10.1016/j.bmc.2010.04.064

  日期：2010.6.15

  A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5'-triphosphate-3'-diphosphate, and ppGpp: 5'-3'-bis-diphosphate), collectively called (p) ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p) ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p) ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2'-Deoxyguanosine-3'-5'-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site.As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. (C) 2010 Elsevier Ltd. All rights reserved.