N-(2-Amino-ethyl)-2-(7-dimethylamino-2-oxo-2H-chromen-4-yl)-acetamide | 861228-86-6

• 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: N-(2-Amino-ethyl)-2-(7-dimethylamino-2-oxo-2H-chromen-4-yl)-acetamide
• 英文别名: N-(2-aminoethyl)-2-[7-(dimethylamino)-2-oxochromen-4-yl]acetamide
• CAS: 861228-86-6
• 化学式: C₁₅H₁₉N₃O₃
• 分子量: 289.334
• InChiKey: YGHAZDXLAWZQQW-UHFFFAOYSA-N

物化性质

• 沸点：
  580.8±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-Amino-ethyl)-2-(7-dimethylamino-2-oxo-2H-chromen-4-yl)-acetamide 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.17h， 生成 (2R)-N-[3-[2-[[2-[7-(dimethylamino)-2-oxochromen-4-yl]acetyl]amino]ethylamino]-3-oxopropyl]-2,4-dihydroxy-3,3-dimethylbutanamide
  参考文献：
  名称：

  One-pot chemo-enzymatic synthesis of reporter-modified proteins

  摘要：

  为了应对蛋白质共价报告标记领域的最新进展，我们提出了一种灵活的报告模拟物合成方法。在此，我们展示了一种一锅法化学酶合成带有报告标记的蛋白质的技术，该技术能够在载体蛋白质或融合构建体上共价连接任何氨基末端荧光或亲和标记。这一双反应序列包括活化的泛酸结合、生物合成转化为辅酶A（CoA）模拟物，以及通过磷酸泛酰巯基乙胺转移酶（PPTase）进行的载体蛋白质修饰。我们还探究了该途径中第一个酶CoAA的底物特异性。通过这种方法，CoA模拟物可以迅速制备，从而允许各种分子种类的报告基团在特定位置进行连接。

  DOI：

  10.1039/b512735a
• 作为产物：
  描述：

  7-二甲氨基香豆素-4-乙酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-(2-Amino-ethyl)-2-(7-dimethylamino-2-oxo-2H-chromen-4-yl)-acetamide
  参考文献：
  名称：

  Fluorescent Profiling of Natural Product Producers

  摘要：

  The identification of natural product producer organisms remains a problem for both isolation and natural product classification. A concise screen is developed through fluorescent modification of a set of natural products that offer a common activity. Through real-time multicolor microscopy, the processing, storage, and effects of a natural product are rapidly screened at the level of the strain and individual organism.

  DOI：

  10.1021/ja042756u

文献信息

• Evaluation of the pharmacophoric motif of the caged Garcinia xanthones
  作者：Oraphin Chantarasriwong、Woo Cheal Cho、Ayse Batova、Warinthorn Chavasiri、Curtis Moore、Arnold L. Rheingold、Emmanuel A. Theodorakis

  DOI：10.1039/b913496d

  日期：——

  The combination of unique structure and potent bioactivity exhibited by several family members of the caged Garciniaxanthones, led us to evaluate their pharmacophore. We have developed a Pd(0)-catalyzed method for the reverse prenylation of catechols that, together with a Claisen/Diels–Alder reaction cascade, provides rapid and efficient access to various caged analogues. Evaluation of the growth inhibitory activity of these compounds leads to the conclusion that the intact ABC ring system containing the C-ring caged structure is essential to the bioactivity. Studies with cluvenone (7) also showed that these compounds induce apoptosis and exhibit significant cytotoxicity in multidrug-resistant leukemia cells. As such, the caged Garciniaxanthone motif represents a new and potent pharmacophore.

  几种带有独特结构和强效生物活性的囊状（caged）Garciniaxanthone家族成员的结合，促使我们评估它们的药效团（pharmacophore）。我们开发了一种Pd(0)催化的方法，用于酚类化合物的反向普雷尼尔化（reverse prenylation），结合Claissen/Diels–Alder反应级联，实现了对各种囊状类似物的快速和高效获取。这些化合物的生长抑制活性评估得出结论，完整的ABC环系统及其C环囊状结构对生物活性至关重要。与克鲁文酮（cluvenone，每个7号的化合物）进行的研究还表明，这些化合物能够诱导细胞凋亡，并在多药耐药性白血病细胞中表现出显著的细胞毒性。因此，囊状Garciniaxanthone结构代表了一种新的强效药效团。
• Irreversible Protein Labeling by Paal-Knorr Conjugation
  作者：Ramesh Dasari、James J. La Clair、Alexander Kornienko

  DOI：10.1002/cbic.201700210

  日期：2017.9.19

  lysines: Recent advances toward a suite of bioorthogonal chemical reactions have profoundly enhanced the tools available to biochemists to study proteins and other biomolecules. Here, we describe the use of the Paal–Knorr reaction to fluorescently label proteins. The described procedures operate without reagents, catalysts, or organic solvents, as needed for a biocompatible method.

  标记赖氨酸：一系列生物正交化学反应的最新进展极大地增强了生物化学家研究蛋白质和其他生物分子的工具。在这里，我们描述了使用Paal-Knorr反应来荧光标记蛋白质。根据生物相容性方法的需要，所描述的程序无需试剂，催化剂或有机溶剂即可运行。
• Active site labeling of fatty acid and polyketide acyl-carrier protein transacylases
  作者：Tony D. Davis、Jennifer M. Michaud、Michael D. Burkart

  DOI：10.1039/c8ob03229g

  日期：——

  Metabolic engineering of fatty acids and polyketides remains challenging due to unresolved protein-protein interactions that are essential to synthase activity. While several chemical probes have been developed to capture and visualize protein interfaces in these systems, acyl carrier protein (ACP) transacylase (AT) domains remain elusive. Herein, we combine a mutational strategy with fluorescent probe

  脂肪酸和聚酮化合物的代谢工程仍然具有挑战性，因为未分解的蛋白质-蛋白质相互作用是合酶活性所必需的。尽管已经开发了几种化学探针来捕获和可视化这些系统中的蛋白质界面，但酰基载体蛋白质（ACP）转酰基酶（AT）域仍然难以捉摸。在本文中，我们将突变策略与荧光探针设计相结合，以加快对脂肪酸和聚酮化合物合酶中AT结构域的研究。我们描述了包含磺酰氟和β-内酯战斗部的抑制剂启发和模拟底物的报道分子的设计和评估。此外，通过优化pH，时间和探针浓度可以进行特定的活性位点标记，并且在存在竞争域抑制剂的情况下可以实现选择性标记。
• PROBE FOR iFRET AND USE THEREOF
  申请人：Chung Sang Jeon

  公开号：US20140242606A1

  公开（公告）日：2014-08-28

  The present invention relates to a probe for iFRET and use thereof. Specifically, the present invention relates to a novel probe for iFRET, a method for preparing the probe for iFRET, a method for searching a target protein-specific binding site or a molecule having the binding site using the probe for iFRET, and a method for imaging the target protein using the probe for iFRET. The probe for iFRET according to the present invention utilizes an amino acid in a protein as a fluorescent donor, unlike the conventional FRET method. Therefore, only one fluorescent material is used, and its emission wavelength is distinct from the intrinsic fluorescence of the protein. Thus, high specificity and sensitivity are ensured, and the quantity, activity and mechanism of various proteins can be analyzed in an easy and accurate manner.

  本发明涉及一种用于iFRET的探针及其使用。具体而言，本发明涉及一种新型iFRET探针、制备iFRET探针的方法、使用iFRET探针搜索靶蛋白特异性结合位点或具有结合位点的分子的方法，以及使用iFRET探针成像靶蛋白的方法。本发明的iFRET探针利用蛋白质中的氨基酸作为荧光给体，而不是传统的FRET方法。因此，仅使用一个荧光材料，其发射波长与蛋白质的内在荧光不同。因此，确保了高度的特异性和灵敏度，并且可以轻松准确地分析各种蛋白质的数量、活性和机制。
• Napyradiomycins CNQ525.510B and A80915C target the Hsp90 paralogue Grp94
  作者：Lauge Farnaes、James J. La Clair、William Fenical

  DOI：10.1039/c3ob41355a

  日期：——

  The intracellular localization and target of the napyradiomycin congeners CNQ525.510B and A80815C were explored using an immunoaffinity fluorescence (IAF) approach. Semi-synthetic methods were used to prepare probes from napyradiomycin CNQ525.510B and derivative A80815C. The results of confocal microscopy indicated that probes from both natural products localized predominantly within the endoplasmic reticulum (ER) of HCT-116 human colon carcinoma cells. Parallel immunoaffinity precipitation efforts using a monoclonal antibody designed against the IAF tag, resulted in the isolation of an Hsp90 family member. This protein was identified as human Grp94 (hGrp94), by its specific mass spectral signature. This observation was validated by Western blot analyses and by the result of an in vitro Grp94 binding assay. The fact that the napyradiomycins CNQ525.510B and A80815C bind to hGrp94, and their associated probes localize within the ER, suggest the use of these materials as molecular probes for monitoring ER-based chaperone function.

  使用免疫亲和荧光（IAF）方法研究了萘拉霉素同系物CNQ525.510B和A80815C的细胞内定位和靶向。使用半合成方法从萘拉霉素CNQ525.510B和衍生物A80815C制备探针。共聚焦显微镜的结果表明，这两种天然产物制备的探针主要定位在HCT-116人结肠癌细胞的内质网（ER）内。使用针对IAF标签设计的一种单克隆抗体进行平行免疫亲和沉淀，结果分离出一种Hsp90家族成员。通过其特定的质谱特征，该蛋白被鉴定为人类Grp94（hGrp94）。这一观察结果通过蛋白质印迹分析和体外Grp94结合分析的结果得到了验证。萘拉霉素CNQ525.510B和A80815C与hGrp94结合，其相关探针定位在内质网内，这表明这些材料可用作监测基于内质网的伴侣功能的分子探针。