sodium ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(prop-2-yn-1-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl morpholinophosphonate | 1585182-45-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: sodium ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(prop-2-yn-1-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl morpholinophosphonate
• CAS: 1585182-45-1
• 化学式: C₁₇H₂₂N₆O₇P*Na
• 分子量: 476.361
• InChiKey: CUGFLDRLGRJOPP-TZNCIMHNSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.69
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  167.15
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  sodium ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(prop-2-yn-1-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl morpholinophosphonate 、 5-ethyl-nicotinamide mononucleotide 在 magnesium sulfate 、 manganese(ll) chloride 作用下， 以 formamide 为溶剂， 反应 48.0h， 以31%的产率得到
  参考文献：
  名称：

  Engineering the Substrate Specificity of ADP-Ribosyltransferases for Identifying Direct Protein Targets

  摘要：

  Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function in both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids of target proteins. The functional redundancy and overlapping target specificities among the 17 ARTDs in humans make the identification of direct targets of individual ARTD family members in a cellular context a formidable challenge. Here we describe the rational design of orthogonal NAD(+) analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. Guided by initial inhibitor studies with nicotinamide analogues containing substituents at the C-5 position, we synthesized an orthogonal NAD(+) variant and found that it is used as a substrate for several engineered ARTDs (ARTD1, -2, and -6) but not their wild-type counterparts. Comparing the target profiles of ARTD1 (PARP1) and ARTD2 (PARP2) in nuclear extracts highlighted the semi-complementary, yet distinct, protein targeting. Using affinity purification followed by tandem mass spectrometry, we identified 42 direct ARTD1 targets and 301 direct ARTD2 targets. This represents a powerful new technique for identifying direct protein targets of individual ARTD family members, which will facilitate studies delineating the pathway from ARTD activation to a given cellular response.

  DOI：

  10.1021/ja412897a
• 作为产物：
  描述：

  N⁶-propargyladenosine 在 磷酸三甲酯 、 2,2'-二硫二吡啶 、 三苯基膦 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.75h， 生成 sodium ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(prop-2-yn-1-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl morpholinophosphonate
  参考文献：
  名称：

  Engineering the Substrate Specificity of ADP-Ribosyltransferases for Identifying Direct Protein Targets

  摘要：

  Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function in both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids of target proteins. The functional redundancy and overlapping target specificities among the 17 ARTDs in humans make the identification of direct targets of individual ARTD family members in a cellular context a formidable challenge. Here we describe the rational design of orthogonal NAD(+) analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. Guided by initial inhibitor studies with nicotinamide analogues containing substituents at the C-5 position, we synthesized an orthogonal NAD(+) variant and found that it is used as a substrate for several engineered ARTDs (ARTD1, -2, and -6) but not their wild-type counterparts. Comparing the target profiles of ARTD1 (PARP1) and ARTD2 (PARP2) in nuclear extracts highlighted the semi-complementary, yet distinct, protein targeting. Using affinity purification followed by tandem mass spectrometry, we identified 42 direct ARTD1 targets and 301 direct ARTD2 targets. This represents a powerful new technique for identifying direct protein targets of individual ARTD family members, which will facilitate studies delineating the pathway from ARTD activation to a given cellular response.

  DOI：

  10.1021/ja412897a