7-(diethylamino)-N-(2-(2-hydroxyethoxy)ethyl)-2-oxo-2H-chromene-3-carboxamide | 1158798-37-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-(diethylamino)-N-(2-(2-hydroxyethoxy)ethyl)-2-oxo-2H-chromene-3-carboxamide
• 英文别名: 7-(diethylamino)-N-[2-(2-hydroxyethoxy)ethyl]-2-oxochromene-3-carboxamide
• CAS: 1158798-37-8
• 化学式: C₁₈H₂₄N₂O₅
• 分子量: 348.399
• InChiKey: XSDPMXMKKKDQRM-UHFFFAOYSA-N

物化性质

• 沸点：
  625.7±55.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-(diethylamino)-N-(2-(2-hydroxyethoxy)ethyl)-2-oxo-2H-chromene-3-carboxamide 在 吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Activity-Based Sensing with a Metal-Directed Acyl Imidazole Strategy Reveals Cell Type-Dependent Pools of Labile Brain Copper

  摘要：

  Copper is a required nutrient for life and particularly important to the brain and central nervous system. Indeed, copper redox activity is essential to maintaining normal physiological responses spanning neural signaling to metabolism, but at the same time copper misregulation is associated with inflammation and neurodegeneration. As such, chemical probes that can track dynamic changes in copper with spatial resolution, especially in loosely bound, labile forms, are valuable tools to identify and characterize its contributions to healthy and disease states. In this report, we present an activity-based sensing (ABS) strategy for copper detection in live cells that preserves spatial information by a copper-dependent bioconjugation reaction. Specifically, we designed copper-directed acyl imidazole dyes that operate through copper-mediated activation of acyl imidazole electrophiles for subsequent labeling of proximal proteins at sites of elevated labile copper to provide a permanent stain that resists washing and fixation. To showcase the utility of this new ABS platform, we sought to characterize labile copper pools in the three main cell types in the brain: neurons, astrocytes, and microglia. Exposure of each of these cell types to physiologically relevant stimuli shows distinct changes in labile copper pools. Neurons display translocation of labile copper from somatic cell bodies to peripheral processes upon activation, whereas astrocytes and microglia exhibit global decreases and increases in intracellular labile copper pools, respectively, after exposure to inflammatory stimuli. This work provides foundational information on cell type-dependent homeostasis of copper, an essential metal in the brain, as well as a starting point for the design of new activity-based probes for metals and other dynamic signaling and stress analytes in biology.

  DOI：

  10.1021/jacs.0c05727

文献信息

• Quenched Ligand-Directed Tosylate Reagents for One-Step Construction of Turn-On Fluorescent Biosensors
  作者：Shinya Tsukiji、Hangxiang Wang、Masayoshi Miyagawa、Tomonori Tamura、Yousuke Takaoka、Itaru Hamachi

  DOI：10.1021/ja902486c

  日期：2009.7.1

  Semisynthetic fluorescent biosensors consisting of a protein framework and a synthetic fluorophore are powerful analytical tools for specific detection of biologically relevant molecules. We report herein a novel method that allows for the construction of turn-on fluorescent semisynthetic biosensors in a one-step manner. The strategy is based on the ligand-directed tosyl (LDT) chemistry, a new type

  由蛋白质框架和合成荧光团组成的半合成荧光生物传感器是用于特异性检测生物相关分子的强大分析工具。我们在此报告了一种允许以一步方式构建开启荧光半合成生物传感器的新方法。该策略基于配体定向甲苯磺酰 (LDT) 化学，这是一种新型的亲和引导蛋白质标记方案，可以将合成探针定点地引入蛋白质表面，同时释放亲和配体。新型淬灭配体定向甲苯磺酸酯 (Q-LDT) 试剂是通过将有机染料连接到蛋白质配体和荧光淬灭剂的偶联物通过甲苯磺酰基接头而设计的。Q-LDT 介导的标记直接将天然蛋白质转化为荧光标记的蛋白质，该蛋白质与裂解的配体栓系猝灭剂保持非共价复合。这种标记蛋白质的荧光最初被淬灭，并且由于配体-淬灭剂片段的排出，只有在特定分析物存在时，荧光才会增强（打开）。使用单个标记步骤，该方法成功应用于碳酸酐酶 II (CAII) 和 Src 同源 2 (SH2) 域，以分别生成针对 CAII 抑制剂和磷酸酪氨酸肽的开
• Site-specific covalent labeling of His-tag fused proteins with a reactive Ni(ii)–NTA probe
  作者：Sho-hei Uchinomiya、Hiroshi Nonaka、Sho-hei Fujishima、Shinya Tsukiji、Akio Ojida、Itaru Hamachi

  DOI：10.1039/b912025d

  日期：——

  A new method for covalent labeling of a His-tag fused protein with a small reactive probe was developed; this method is based on the complementary interaction between the His-tag and Ni(II)–NTA, which facilitates a nucleophilic reaction between a histidine residue of the tag and the electrophilictosyl group of the Ni(II)–NTA probe by the proximity effect.

  该方法基于His标签与Ni(II)âNTA之间的互补作用，通过邻近效应促进标签的组氨酸残基与Ni(II)âNTA探针的亲电基之间发生亲核反应。
• Coumarin-based compounds and related methods
  申请人：Biosearch Technologies, Inc.

  公开号：US11034677B2

  公开（公告）日：2021-06-15

  The present invention generally relates to coumarin-based compounds that can be used for the labeling of biological molecules, as well as related synthetic and testing methods. The coumarin-based compounds typically survive conditions necessary for automated synthesis of nucleic acids without undergoing any substantial degree of degradation or alteration.

  本发明一般涉及可用于标记生物分子的香豆素基化合物以及相关的合成和测试方法。香豆素基化合物通常能在核酸自动合成所需的条件下存活，而不会发生任何程度的降解或改变。
• Native FKBP12 Engineering by Ligand-Directed Tosyl Chemistry: Labeling Properties and Application to Photo-Cross-Linking of Protein Complexes in Vitro and in Living Cells
  作者：Tomonori Tamura、Shinya Tsukiji、Itaru Hamachi

  DOI：10.1021/ja209641t

  日期：2012.2.1

  The ability to modify target "native" (endogenous) proteins selectively in living cells with synthetic molecules should provide powerful tools for chemical biology. To this end, we recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chemistry. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. We previously demonstrated its applicability to the selective chemical labeling of several native proteins in living cells and mice. However, many fundamental features of this chemistry remain to be studied. In this work, we investigated the relationship between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro experiments revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addition to histidine, which we reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was found to be optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent containing a photoreactive probe, we successfully demonstrated the labeling and UV-induced covalent cross-linking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers our understanding of the basic reaction properties of LDT chemistry but also extends the applicability of this method to the investigation of biological processes in mammalian cells.
• A Small Molecule That Binds to an ATPase Domain of Hsc70 Promotes Membrane Trafficking of Mutant Cystic Fibrosis Transmembrane Conductance Regulator
  作者：Hyungseoph J. Cho、Heon Yung Gee、Kyung-Hwa Baek、Sung-Kyun Ko、Jong-Moon Park、Hookeun Lee、Nam-Doo Kim、Min Goo Lee、Injae Shin

  DOI：10.1021/ja206762p

  日期：2011.12.21

  Cystic fibrosis transmembrane conductance regulator (CFTR) is a cell-surface anion channel that permeates chloride and bicarbonate ions. The most frequent mutation of CFTR that causes cystic fibrosis is the deletion of phenylalanine at position 508 (Delta F508), which leads to defects in protein folding and cellular trafficking to the plasma membrane. The lack of the cell-surface CFTR results in a reduction in the lifespan due to chronic lung infection with progressive deterioration of lung function. Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. To date, various Hsc70 inhibitors and transcription regulators have been tested to determine whether they correct the defective activity of mutant CFTR However, they exhibited limited or questionable effects on restoring the chloride channel activity in cystic fibrosis cells. Herein, we show that a small molecule apoptozole (Az) has high cellular potency to promote membrane trafficking of mutant CFTR and its chloride channel activity in cystic fibrosis cells. Results from affinity chromatography and ATPase activity assay indicate that Az inhibits the ATPase activity of Hsc70 by binding to its ATPase domain. In addition, a ligand-directed protein labeling and molecular modeling studies also suggest the binding of Az to an ATPase domain, in particular, an ATP-binding pocket. It is proposed that Az suppresses ubiquitination of Delta F508-CFTR maybe by blocking interaction of the mutant with Hsc70 and CHIP, and, as a consequence, it enhances membrane trafficking of the mutant.