5-[3,3-Dimethyl-2-[3-(1,3,3-trimethylindol-1-ium-2-yl)prop-2-enylidene]indol-1-yl]pentanoic acid | 1043687-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-[3,3-Dimethyl-2-[3-(1,3,3-trimethylindol-1-ium-2-yl)prop-2-enylidene]indol-1-yl]pentanoic acid
• 英文别名: 5-[3,3-dimethyl-2-[3-(1,3,3-trimethylindol-1-ium-2-yl)prop-2-enylidene]indol-1-yl]pentanoic acid
• CAS: 1043687-16-6
• 化学式: C₂₉H₃₅N₂O₂
• 分子量: 443.609
• InChiKey: PRSUSTFQLNVYDB-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[3,3-Dimethyl-2-[3-(1,3,3-trimethylindol-1-ium-2-yl)prop-2-enylidene]indol-1-yl]pentanoic acid 、 N-(2-aminoethyl)pent-4-ynamide 在 N,N-二异丙基乙胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以13 mg的产率得到
  参考文献：
  名称：

  Ratiometric analysis of zidovudine (ZDV) incorporation by reverse transcriptases or polymerases via bio-orthogonal click chemistry

  摘要：

  一种新的基于荧光的检测方法被开发出来，用于通过点击化学法可视化含有齐多夫定的DNA。这种生物正交检测方法用于量化不同DNA合成酶对ZDV掺入的相对敏感性，依据是凝胶中条带位移的比率分析以及细胞DNA的可视观察。

  DOI：

  10.1039/c1cc12518d

文献信息

• Selective affinity-based probe for oncogenic kinases suitable for live cell imaging
  作者：Claudio Zambaldo、Kalyan K. Sadhu、Ganesan Karthikeyan、Sofia Barluenga、Jean-Pierre Daguer、Nicolas Winssinger

  DOI：10.1039/c3sc21856b

  日期：——

  Cell permeable probes to image the presence and localization of kinases are important in studying their function and as diagnostic tools. Despite the central role of kinases as therapeutic targets, there are remarkably few probes available. Herein we report the discovery of a probe to image two therapeutically relevant kinases: EGFR and ERBB2. The probe was identified from a library based on a scaffold derived from the resorcyclic acid lactones that form a covalent adduct by reacting specifically with an unconserved cysteine in the nucleotide-binding site of the kinases. We demonstrated the utility of the newly discovered probe by imaging of EGFR localization and ERBB2 inhibition in live cells.

  在研究激酶的功能和将其作为诊断工具时，对激酶的存在和定位进行成像的细胞渗透探针非常重要。尽管激酶作为治疗靶点发挥着核心作用，但可用的探针却少得可怜。在此，我们报告发现了一种探针，可以对两种与治疗相关的激酶进行成像：表皮生长因子受体和 ERBB2。这种探针是从一个文库中发现的，该文库的基础是一种源自间环酸内酯的支架，间环酸内酯通过与激酶核苷酸结合位点中未保留的半胱氨酸发生特异性反应而形成共价加合物。我们通过对活细胞中表皮生长因子受体定位和ERBB2抑制作用的成像，证明了新发现探针的实用性。
• OLIGONUCLEOTIDE PROBE AND USE THEREOF
  申请人：ASANUMA Hiroyuki

  公开号：US20110229980A1

  公开（公告）日：2011-09-22

  The present teaching provides a fluorescent oligonucleotide probe having a high degree of design flexibility and wide applicability, as well as the use thereof. This is an oligonucleotide probe capable of forming a stem and loop, comprising at least one fluorophore located between adjacent nucleotides in the stem and is linked to a unit represented by Formula (1) and at least one quencher located at a site capable of pairing up with the at least one fluorophore located between the adjacent nucleotides in the stem and is linked to a unit represented by Formula (2). (In the formulae, X represents the fluorophore, Y represents the quencher, R1 represents an optionally substituted C 2 or C 3 alkylene chain, R2 represents an optionally substituted C 0-2 alkylene chain, and Z represents a direct bond or linker.)

  本教学提供了一种具有高度设计灵活性和广泛适用性的荧光寡核苷酸探针及其使用。这是一种能够形成茎环的寡核苷酸探针，包括至少一个荧光物质位于茎中相邻核苷酸之间，并与由式（1）表示的单元连接，以及至少一个淬灭剂位于能够与茎中相邻核苷酸之间的至少一个荧光物质配对的位置，并与由式（2）表示的单元连接。（在公式中，X代表荧光物质，Y代表淬灭剂，R1代表可选择地取代的C2或C3烷基链，R2代表可选择地取代的C0-2烷基链，Z代表直接键或连接物。）
• Coherent Quenching of a Fluorophore for the Design of a Highly Sensitive In-Stem Molecular Beacon
  作者：Yuichi Hara、Taiga Fujii、Hiromu Kashida、Koji Sekiguchi、Xingguo Liang、Kosuke Niwa、Tomokazu Takase、Yasuko Yoshida、Hiroyuki Asanuma

  DOI：10.1002/anie.201001459

  日期：——

  Excitonic interaction was utilized to design a highly sensitive in‐stem molecular beacon (ISMB) in which both a fluorophore and a quencher on D‐threoninols are incorporated as a pseudo base pair (see scheme; optimized combination with Cy3 and modified Methyl Red). Minimization of the difference between λmax of the fluorophore and quencher maximized quenching efficiency.

  利用激子相互作用设计了一个高度敏感的系统内分子信标（ISMB），其中将D-苏氨酸上的荧光团和猝灭剂都作为假碱基对掺入（见方案；与Cy3和修饰的甲基红的优化组合）。之间的差的最小化λ最大荧光团的淬灭剂和最大化淬火效率。
• 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.