adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
• 英文别名: ADP-HPD；5'-O-[(S)-{[(S)-{[(2R,3R,4S)-3,4-Dihydroxypyrrolidin-2-YL]methoxy}(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]adenosine；[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl]methyl hydrogen phosphate
• 化学式: C₁₅H₂₄N₆O₁₂P₂
• 分子量: 542.336
• InChiKey: NDQDTBCXPOIQGT-UHNJQBFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -8.2
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  274
• 氢给体数：
  8
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-ADP-HPD 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 生成 adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
  参考文献：
  名称：

  Specific Inhibition of Poly(ADP-ribose) Glycohydrolase by Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol

  摘要：

  Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), an NH analog of ADP-ribose, was chemically synthesized and shown to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. The synthetic starting material was the protected pyrroidine, (2R,3R,4S)-1-(benzyloxycarbonyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal. This starting pyrrolidine was phosphorylated, coupled to adenosine 5'-monophosphate, and deprotected, yielding the title inhibitor ADP-HPD. ADP-HDP was shown to inhibit the activity of poly(ADP-ribose) glycohydrolase by 50% (IC50) at 0.12 mu M, a value 1000-times lower than the IC50 of the product, ADP-ribose. The NAD glycohydrolase from Bungarus fasciatus venom was less sensitive to inhibition by ADP-HPD,exhibiting an IC50 of 260 mu M. ADP-HPD did not inhibit either poly(ADP-ribose) polymerase or NAD:arginine mono(ADP-ribosyl)-transferase A at inhibitor concentrations up to 1 mM. At low ADP-HPD concentration, inhibition was therefore shown to be highly specific for poly(ADP-ribose) glycohydrolase,the hydrolytic enzyme in the metabolism of ADP-ribose polymers.

  DOI：

  10.1021/jm00002a021

文献信息

• Specific Inhibition of Poly(ADP-ribose) Glycohydrolase by Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol
  作者：James T. Slama、Nasreen Aboul-Ela、Deepa M. Goli、Bruce V. Cheesman、Anne M. Simmons、Myron K. Jacobson

  DOI：10.1021/jm00002a021

  日期：1995.1

  Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), an NH analog of ADP-ribose, was chemically synthesized and shown to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. The synthetic starting material was the protected pyrroidine, (2R,3R,4S)-1-(benzyloxycarbonyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal. This starting pyrrolidine was phosphorylated, coupled to adenosine 5'-monophosphate, and deprotected, yielding the title inhibitor ADP-HPD. ADP-HDP was shown to inhibit the activity of poly(ADP-ribose) glycohydrolase by 50% (IC50) at 0.12 mu M, a value 1000-times lower than the IC50 of the product, ADP-ribose. The NAD glycohydrolase from Bungarus fasciatus venom was less sensitive to inhibition by ADP-HPD,exhibiting an IC50 of 260 mu M. ADP-HPD did not inhibit either poly(ADP-ribose) polymerase or NAD:arginine mono(ADP-ribosyl)-transferase A at inhibitor concentrations up to 1 mM. At low ADP-HPD concentration, inhibition was therefore shown to be highly specific for poly(ADP-ribose) glycohydrolase,the hydrolytic enzyme in the metabolism of ADP-ribose polymers.