2-((E)-3-((E)-3,3-dimethyl-1-(3-phenylpropyl)indolin-2-ylidene)prop-1-en-1-yl)-3,3-dimethyl-1-(3-phenylpropyl)-3H-indol-1-ium bromide | 1388714-12-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((E)-3-((E)-3,3-dimethyl-1-(3-phenylpropyl)indolin-2-ylidene)prop-1-en-1-yl)-3,3-dimethyl-1-(3-phenylpropyl)-3H-indol-1-ium bromide
• 英文别名: 1-(3-phenylpropyl)-2-((1E,3E)-3-(1-(3-phenylpropyl)-3,3-dimethylindolin-2-ylidene)prop-1-en-1-yl)-3,3-dimethyl-3H-indol-1-ium bromide；E-4；2-[3-[3,3-dimethyl-1-(3-phenylpropyl)indol-1-ium-2-yl]prop-2-enylidene]-3,3-dimethyl-1-(3-phenylpropyl)indole;bromide
• CAS: 1388714-12-2
• 化学式: Br*C₄₁H₄₅N₂
• 分子量: 645.726
• InChiKey: ZJBJPSWQWWNTHT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.57
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  6.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-甲基-2-丁酮 在 乙酸酐 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 72.5h， 生成 2-((E)-3-((E)-3,3-dimethyl-1-(3-phenylpropyl)indolin-2-ylidene)prop-1-en-1-yl)-3,3-dimethyl-1-(3-phenylpropyl)-3H-indol-1-ium bromide
  参考文献：
  名称：

  Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

  摘要：

  多种菁染料作为DNA染料和传感器具有多功能性和灵敏性，并已通过结构修饰，以序列依赖的方式结合于DNA小沟。同样，我们正在开发一套新的菁染料，这些染料被设计用于高度选择性地结合DNA G-四链体，而对DNA双链的结合力较弱。系统地合成了结构类似的三甲川菁染料并评估了其对四链体的靶向作用。结果显示，增强四链体结合和特异性对多甲川链长度、杂环结构和化合物的固有电荷非常敏感。生物物理实验表明，这些化合物对四链体结合表现出显著的选择性，更偏好于平行链四链体，如cMYC。核磁共振研究揭示了主要通过末端堆积模式结合，表面等离子体共振研究显示最强的化合物主要的解离常数值低于100 nM，而对双链体的结合力几乎弱了100倍。这些新设计的三甲川菁染料对四链体的高度选择性以及它们区分不同四链体的能力是非常有前景的特性，有望开发它们作为体内靶向四链体的新型探针。

  DOI：

  10.3390/molecules181113588

文献信息

• Synthesis and evaluation of carbocyanine dyes as PRMT inhibitors and imaging agents
  作者：Sarmistha Halder Sinha、Eric A. Owens、You Feng、Yutao Yang、Yan Xie、Yaping Tu、Maged Henary、Yujun George Zheng

  DOI：10.1016/j.ejmech.2012.06.017

  日期：2012.8

  Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines
  作者：Rupesh Nanjunda、Eric Owens、Leah Mickelson、Tyler Dost、Ekaterina Stroeva、Hang Huynh、Markus Germann、Maged Henary、W. Wilson

  DOI：10.3390/molecules181113588

  日期：——

  A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo.

  多种菁染料作为DNA染料和传感器具有多功能性和灵敏性，并已通过结构修饰，以序列依赖的方式结合于DNA小沟。同样，我们正在开发一套新的菁染料，这些染料被设计用于高度选择性地结合DNA G-四链体，而对DNA双链的结合力较弱。系统地合成了结构类似的三甲川菁染料并评估了其对四链体的靶向作用。结果显示，增强四链体结合和特异性对多甲川链长度、杂环结构和化合物的固有电荷非常敏感。生物物理实验表明，这些化合物对四链体结合表现出显著的选择性，更偏好于平行链四链体，如cMYC。核磁共振研究揭示了主要通过末端堆积模式结合，表面等离子体共振研究显示最强的化合物主要的解离常数值低于100 nM，而对双链体的结合力几乎弱了100倍。这些新设计的三甲川菁染料对四链体的高度选择性以及它们区分不同四链体的能力是非常有前景的特性，有望开发它们作为体内靶向四链体的新型探针。