N’-(2,3,5-tri-o-benzoyl-β-D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide | 1585182-46-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N’-(2,3,5-tri-o-benzoyl-β-D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide
• CAS: 1585182-46-2
• 化学式: Br*C₃₄H₃₁N₂O₈
• 分子量: 675.533
• InChiKey: LMIFEQFZZMXIPF-JDMQWPEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.84
• 重原子数：
  45.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  135.1
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N’-(2,3,5-tri-o-benzoyl-β-D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide 在 甲醇 、 氨 作用下， 反应 36.0h， 以71%的产率得到N’-(D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide
  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：

  5-vinyl-nicotinamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 53.0h， 生成 N’-(2,3,5-tri-o-benzoyl-β-D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide
  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