4′,5′-bis(1,3,2-dithioarsolan-2-yl) fluorescein | 212118-77-9

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4′,5′-bis(1,3,2-dithioarsolan-2-yl) fluorescein
• 英文别名: Fluorescein Arsenical Hairpin Binder；Lumio Green；2-[4,5-bis(1,3,2-dithiarsolan-2-yl)-3-hydroxy-6-oxoxanthen-9-yl]benzoic acid
• CAS: 212118-77-9
• 化学式: C₂₄H₁₈As₂O₅S₄
• 分子量: 664.511
• InChiKey: KCPRYVGBEBFLIG-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：15mg/mL； DMSO：20mg/mL； DMSO:PBS (pH 7.2) (1:10)：0.09 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  185
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4′,5′-bis(1,3,2-dithioarsolan-2-yl) fluorescein 在 mercury(II) diacetate 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 以34%的产率得到4',5'-bis-(arsenoso)fluorescein
  参考文献：
  名称：

  New Biarsenical Ligands and Tetracysteine Motifs for Protein Labeling in Vitro and in Vivo:  Synthesis and Biological Applications

  摘要：

  We recently introduced a method (Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269-272 and Griffin, B. A.; Adams, S. R.; Jones, J.; Tsien, R. Y. Methods Enzymol. 2000, 327,565-578) for site-specific fluorescent labeling of recombinant proteins in living cells. The sequence Cys-Cys-Xaa-Xaa-Cys-Cys, where Xaa is an noncysteine amino acid, is genetically fused to or inserted within the protein, where it can be specifically recognized by a membrane-permeant fluorescein derivative with two As(III) substituents, RASH, which fluoresces only after the arsenics bind to the cysteine thiols. We now report kinetics and dissociation constants (similar to10(-11) M) for FIAsH binding to model tetracysteine peptides. Affinities in vitro and detection limits in living cells are optimized with Xaa-Xaa = Pro-Gly, suggesting that the preferred peptide conformation is a hairpin rather than the previously proposed alpha-helix. Many analogues of RASH have been synthesized, including ReAsH, a resorufin derivative excitable at 590 nm and fluorescing in the red. Analogous biarsenicals enable affinity chromatography, fluorescence anisotropy measurements, and electron-microscopic localization of tetracysteine-tagged proteins.

  DOI：

  10.1021/ja017687n
• 作为产物：
  描述：

  fluorescein free acid 在 palladium diacetate 、 三氯化砷 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 7.0h， 生成 4′,5′-bis(1,3,2-dithioarsolan-2-yl) fluorescein
  参考文献：
  名称：

  用双砷探针探查靶蛋白对敏感蛋白酪氨酸磷酸酶的抑制作用†

  摘要：

  酶活性的选择性控制对于阐明特定蛋白在信号通路中的作用至关重要。开发真正的靶标特异性抑制剂的一种潜在手段包括使用蛋白质工程技术使靶标酶对不抑制同源野生型酶的小分子产生抑制作用。以前，已经显示蛋白质酪氨酸磷酸酶（PTP）可以被双砷探针FlAsH-EDT 2抑制。，通过与已引入催化重要区域的半胱氨酸残基特异性结合来抑制PTP活性。在本研究中，我们开发了一系列双砷探针，其中一些是新合成的，一些先前已报道过，以首次研究双砷抑制PTP的构效关系。我们的数据表明，在2'和7'位置含有取代的双砷探针在抑制致敏PTP方面比FlAsH-EDT 2更有效。当同时使用两种对位试剂测定PTP时，观察到2'，7'-取代探针的效力增加-硝基苯基磷酸酯和磷酸肽PTP底物，并且处于多个探针浓度。数据进一步表明，增强的抑制特性是2'，7'-取代的双砷探针与致敏PTP之间结合亲和力提高的结果。此外，我们为各种双砷探针提供了以前未知的理化和稳定性数据。

  DOI：

  10.1039/c4ob02256d

文献信息

• A Platform for the Detection of Trypanosomes via Selective Small Molecule Recognition
  作者：Ellen D. Beaulieu、Lori L. Olson、Mary J. Tanga

  DOI：10.1021/ml2000092

  日期：2011.7.14

  Trypanothione (TSH2), a metabolite unique to trypanosomal parasites, was evaluated as a potential biomarker for trypanosomal infection using fluorescence as the means of detection. Fluoroescein arsenical helix binder (FLASH) was prepared and used to detect TSH2. Since it has low background fluorescence and forms a highly emissive complex with TSH2, it can be used to detect low micromolar concentrations of TSH2 in serum. The large dynamic range of FLASH and its selectivity for detection of the dithiol metabolite indicate that arsenical probes may offer a promising new platform for the diagnosis of trypanosomal infection.
• Probing the target-specific inhibition of sensitized protein tyrosine phosphatases with biarsenical probes
  作者：Adam Pomorski、Justyna Adamczyk、Anthony C. Bishop、Artur Krężel

  DOI：10.1039/c4ob02256d

  日期：——

  Selective control of enzyme activity is critical for elucidating the roles of specific proteins in signaling pathways. One potential means for developing truly target-specific inhibitors involves the use of protein engineering to sensitize a target enzyme to inhibition by a small molecule that does not inhibit homologous wild-type enzymes. Previously, it has been shown that protein tyrosine phosphatases

  酶活性的选择性控制对于阐明特定蛋白在信号通路中的作用至关重要。开发真正的靶标特异性抑制剂的一种潜在手段包括使用蛋白质工程技术使靶标酶对不抑制同源野生型酶的小分子产生抑制作用。以前，已经显示蛋白质酪氨酸磷酸酶（PTP）可以被双砷探针FlAsH-EDT 2抑制。，通过与已引入催化重要区域的半胱氨酸残基特异性结合来抑制PTP活性。在本研究中，我们开发了一系列双砷探针，其中一些是新合成的，一些先前已报道过，以首次研究双砷抑制PTP的构效关系。我们的数据表明，在2'和7'位置含有取代的双砷探针在抑制致敏PTP方面比FlAsH-EDT 2更有效。当同时使用两种对位试剂测定PTP时，观察到2'，7'-取代探针的效力增加-硝基苯基磷酸酯和磷酸肽PTP底物，并且处于多个探针浓度。数据进一步表明，增强的抑制特性是2'，7'-取代的双砷探针与致敏PTP之间结合亲和力提高的结果。此外，我们为各种双砷探针提供了以前未知的理化和稳定性数据。
• New Biarsenical Ligands and Tetracysteine Motifs for Protein Labeling in Vitro and in Vivo:  Synthesis and Biological Applications
  作者：Stephen R. Adams、Robert E. Campbell、Larry A. Gross、Brent R. Martin、Grant K. Walkup、Yong Yao、Juan Llopis、Roger Y. Tsien

  DOI：10.1021/ja017687n

  日期：2002.5.1

  We recently introduced a method (Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269-272 and Griffin, B. A.; Adams, S. R.; Jones, J.; Tsien, R. Y. Methods Enzymol. 2000, 327,565-578) for site-specific fluorescent labeling of recombinant proteins in living cells. The sequence Cys-Cys-Xaa-Xaa-Cys-Cys, where Xaa is an noncysteine amino acid, is genetically fused to or inserted within the protein, where it can be specifically recognized by a membrane-permeant fluorescein derivative with two As(III) substituents, RASH, which fluoresces only after the arsenics bind to the cysteine thiols. We now report kinetics and dissociation constants (similar to10(-11) M) for FIAsH binding to model tetracysteine peptides. Affinities in vitro and detection limits in living cells are optimized with Xaa-Xaa = Pro-Gly, suggesting that the preferred peptide conformation is a hairpin rather than the previously proposed alpha-helix. Many analogues of RASH have been synthesized, including ReAsH, a resorufin derivative excitable at 590 nm and fluorescing in the red. Analogous biarsenicals enable affinity chromatography, fluorescence anisotropy measurements, and electron-microscopic localization of tetracysteine-tagged proteins.