5-ethyl-nicotinamide mononucleotide | 1585182-48-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 5-ethyl-nicotinamide mononucleotide
• CAS: 1585182-48-4
• 化学式: C₁₃H₁₉N₂O₈P
• 分子量: 362.276
• InChiKey: QLWDYYUMZGOKJY-PRULPYPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.27
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  166.25
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5-ethyl-nicotinamide mononucleotide 在 magnesium sulfate 、 manganese(ll) chloride 作用下， 以 formamide 为溶剂， 以32 %的产率得到
  参考文献：
  名称：

  脱硫生物素标记的 NAD+ 类似物可揭示聚 (ADP-核糖) 聚合酶 1 蛋白靶点

  摘要：

  揭示 PARP 选择性蛋白靶点对于更好地了解 ADP 核糖基化至关重要。在这里，我们报告了一种新型化学修饰的 NAD +类似物，可应用于 PARP1 的“凹凸-孔”策略。该类似物的烟酰胺部分带有一个乙基（“凸块”），可提高对 PARP1 突变体的选择性。连接到腺嘌呤部分的亲和标签能够对 PARP1 特异性 ADP 核糖基化靶标进行亲和富集。

  DOI：

  10.1002/cbic.202300797
• 作为产物：
  描述：

  N’-(D-ribofuranosyl)-3-aminocarbonyl-5-ethyl-pyridinium bromide 在 磷酸三甲酯 、 三氯氧磷 作用下， 反应 4.0h， 以74%的产率得到5-ethyl-nicotinamide mononucleotide
  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