2-[4-[(3-Methyl-1,3-benzothiazol-2-ylidene)methyl]quinolin-1-ium-1-yl]acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-[4-[(3-Methyl-1,3-benzothiazol-2-ylidene)methyl]quinolin-1-ium-1-yl]acetic acid
• 英文别名: 2-[4-[(3-methyl-1,3-benzothiazol-2-ylidene)methyl]quinolin-1-ium-1-yl]acetic acid
• 化学式: C₂₀H₁₇N₂O₂S
• 分子量: 349.433
• InChiKey: PXAYCAZEKBTDFT-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-[(3-Methyl-1,3-benzothiazol-2-ylidene)methyl]quinolin-1-ium-1-yl]acetic acid 在 N-甲基吗啉 、 吡啶 、 四丁基氟化铵 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 4-甲基苯磺酸吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Brightness Enhanced DNA FIT-Probes for Wash-Free RNA Imaging in Tissue

  摘要：

  Fluorogenic oligonucleotides enable RNA imaging in cells and tissues. A high responsiveness of fluorescence is required when unbound probes cannot be washed away. Furthermore, emission should be bright in order to enable detection against autofluorescent background. The development of fluorescence-quenched hybridization probes has led to remarkable improvement of fluorescence responsiveness. Yet, comparably little attention has been paid to the brightness of smart probes. We describe hybridization probes that combine responsiveness with a high brightness of the measured signal. The method relies upon quencher-free DNA forced intercalation (FIT)-probes, in which two (or more) intercalator dyes of the thiazole orange (TO) family serve as nucleobase surrogates. Initial experiments on multi-TO-labeled probes led to improvements of responsiveness, but self-quenching limited their brightness. To enhance both brightness and responsiveness the highly responsive TO nucleoside was combined with the highly emissive oxazolopyridine analogue JO. Single-stranded TO/JO FIT-probes are dark. In the probe-target duplex, quenching caused by torsional twisting and dye-dye contact is prevented. The TO nucleoside appears to serve as a light collector that increases the extinction coefficient and transfers excitation energy to the JO emitter. This leads to very bright JO emission upon hybridization (F/F-0 = 23, brightness = 43 mL mol(-1) cm(-1) at lambda(ex) = 516 nm). TO/JO FIT-probes allowed the direct fluorescence microscopic imaging of oskar mRNA within a complex tissue. Of note, RNA imaging was feasible under wide-field excitation conditions. The described protocol enables rapid RNA imaging in tissue without the need for cutting-edge equipment, time-consuming washing, or signal amplification.

  DOI：

  10.1021/ja410674h
• 作为产物：
  描述：

  2-甲硫基苯并噻唑 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 2-[4-[(3-Methyl-1,3-benzothiazol-2-ylidene)methyl]quinolin-1-ium-1-yl]acetic acid
  参考文献：
  名称：

  Fluorescence switchable probes based on a molecular rotor for selective detection of proteins and small molecules

  摘要：

  在目标蛋白质的存在下，拥挤的环境会限制荧光分子转子的键转动，从而触发强烈荧光，而添加竞争性配体后应该会减少荧光。

  DOI：

  10.1039/c5cc06714f

文献信息

• 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。）
• Divergent and Linear Solid-Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base
  作者：Dilip V. Jarikote、Olaf Köhler、Elke Socher、Oliver Seitz

  DOI：10.1002/ejoc.200500201

  日期：2005.8

  or base surrogates are to be evaluated. Herein, a method for divergent solid-phase synthesis is presented that serves the purpose to facilitate the screening for base surrogates that fluoresce upon hybridization. An Fmoc/Aloc-protected submonomer allowed the application of commonly used Fmoc-based solid-phase synthesis protocols while removal of the fully orthogonal Aloc group enabled the on-resin introduction

  荧光核碱基替代物为核酸提供了有趣的特性。我们最近将噻唑橙作为碱基替代物引入 PNA，并发现所谓的 FIT（噻唑橙强制插层）PNA 探针通过增强荧光来探测信号杂交。修饰核碱基或引入核碱基替代物的常见方法利用已在溶液相中合成的单体构建块的使用。如果要评估多个基础修改或基础替代品，则需要预制基础修改构建块可能会阻碍进度。在此，提出了一种发散固相合成方法，其目的是促进筛选在杂交时发出荧光的碱基替代物。Fmoc/Aloc 保护的亚单体允许应用常用的基于 Fmoc 的固相合成方案，同时去除完全正交的 Aloc 基团能够在线性链组装完成后在树脂上引入碱基替代物。发散固相合成策略是可自动化的，提供与线性固相合成相匹配的总产量，最重要的是，可以快速访问任何类型的碱基修饰的 PNA。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
• COMPOUND HAVING STRUCTURE DERIVED FROM MONONUCLEOSIDE OR MONONUCLEOTIDE, NUCLEIC ACID, LABELING SUBSTANCE, AND METHOD AND KIT FOR DETECTION OF NUCLEIC ACID
  申请人：Okamoto Akimitsu

  公开号：US20100092971A1

  公开（公告）日：2010-04-15

  The present invention provides, for example, a labeling substance that allows the double helix structure of a nucleic acid to be detected effectively. The present invention provides a compound having a structure derived from mononucleoside or mononucleotide, with the structure being represented by the following formula (1), (1b), or (1c), a tautomer or stereoisomer thereof, or a salt thereof. In the above formulae, B is an atomic group having a nucleobase skeleton, E is an atomic group having a deoxyribose skeleton, a ribose skeleton, or a structure derived from either one of them, or an atomic group having a peptide structure or a peptoid structure, and Z 11 and Z 12 each are a hydrogen atom, a protecting group, or an atomic group that exhibits fluorescence and may be identical to or different from each other.

  本发明提供了一种标记物质，例如，可以有效检测核酸的双螺旋结构。本发明提供了一种化合物，其结构源自单核苷酸或单核苷酸，该结构由以下公式（1），（1b）或（1c）表示，其互变异构体或立体异构体，或其盐。在上述公式中，B是具有核碱基骨架的原子基团，E是具有脱氧核糖骨架，核糖骨架或从它们中的任何一个派生的结构的原子基团，或具有肽结构或肽酰基结构的原子基团，而Z11和Z12分别是氢原子，保护基或具有荧光并且可以相同或不同的原子基团。
• New cyanine dyes as base surrogates in PNA: Forced intercalation probes (FIT-probes) for homogeneous SNP detection
  作者：Lucas Bethge、Dilip Venkatrao Jarikote、Oliver Seitz

  DOI：10.1016/j.bmc.2006.12.044

  日期：2008.1

  Forced intercalation probes (FIT-probes) are nucleic acid probes, in which an intercalator cyanine dye such as thiazole orange (TO) serves as a replacement of a canonical nucleobase. These probes signal hybridization by showing strong increases of fluorescence. TO in FIT-probes responds to adjacent base mismatches by attenuation of fluorescence intensities at conditions where both matched and mismatched target DNA are bound. The interesting features of TO labeled FIT-probes posed the question whether the forced intercalation concept can be extended to other cyanine dyes of the thiazole orange family. Herein, we present the synthesis of three asymmetrical cyanine dyes and their incorporation into PNA-conjugates by means of both divergent and linear solid-phase synthesis. Melting analysis revealed that the DNA affinity of PNA probes remained high irrespective of the replacement of a nucleobase by the cyanines YO (oxazole yellow), MO or JO. Of the three new tested dye-PNA-conjugates, the YO-containing PNA has properties useful for homogeneous SNP detection. YO-PNA is demonstrated to signal the presence of fully complementary DNA by up to 20-fold enhancement of fluorescence. In addition, YO emission discriminates against single base mismatches by attenuation of fluorescence. Oxazole yellow (YO) as a base surrogate in PNA may prove useful in the multiplex detection of single base mutations at non-stringent conditions. (C) 2007 Elsevier Ltd. All rights reserved.
• Fluorescence Detection of <i>KRAS2</i> mRNA Hybridization in Lung Cancer Cells with PNA-Peptides Containing an Internal Thiazole Orange
  作者：Mahesh V. Sonar、Matthew E. Wampole、Yuan-Yuan Jin、Chang-Po Chen、Mathew L. Thakur、Eric Wickstrom

  DOI：10.1021/bc500304m

  日期：2014.9.17

  We previously developed reporter-peptide nucleic acid (PNA)-peptides for sequence-specific radioimaging and fluorescence imaging of particular mRNAs in cells and tumors. However, a direct test for PNA-peptide hybridization with RNA in the cytoplasm would be desirable. Thiazole orange (TO) dye at the 5' end of a hybridization agent shows a strong increase in fluorescence quantum yield when stacked upon a 5' terminal base pair, in solution and in cells. We hypothesized that hybridization agents with an internal TO could distinguish a single base mutation in RNA. Thus, we designed KRAS2 PNA-IGF1 tetrapeptide agents with an internal TO adjacent to the middle base of the 12th codon, a frequent site of cancer-initiating mutations. Our molecular dynamics calculations predicted a disordered bulge with weaker hybridization resulting from a single RNA mismatch. We observed that single-stranded PNA-IGF1 tetrapeptide agents with an internal TO showed low fluorescence, but fluorescence escalated 5-6-fold upon hybridization with KRAS2 RNA. Circular dichroism melting curves showed ∼10 °C higher Tm for fully complementary vs single base mismatch TO-PNA-peptide agent duplexes with KRAS2 RNA. Fluorescence measurements of treated human lung cancer cells similarly showed elevated cytoplasmic fluorescence intensity with fully complementary vs single base mismatch agents. Sequence-specific elevation of internal TO fluorescence is consistent with our hypothesis of detecting cytoplasmic PNA-peptide:RNA hybridization if a mutant agent encounters the corresponding mutant mRNA.