N-[6'-[(2,4-dinitrophenyl)sulfonylamino]-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl]acetamide | 1331849-43-4

• 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: N-[6'-[(2,4-dinitrophenyl)sulfonylamino]-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl]acetamide
• CAS: 1331849-43-4
• 化学式: C₂₈H₁₈N₄O₁₀S
• 分子量: 602.538
• InChiKey: UFNGVTFRHGKEAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  211
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 吡啶 、 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 N-[6'-[(2,4-dinitrophenyl)sulfonylamino]-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl]acetamide
  参考文献：
  名称：

  Synthesis and Characterization of a Series of Highly Fluorogenic Substrates for Glutathione Transferases, a General Strategy

  摘要：

  Glutathione transferases (GSTs) are used in biotechnology applications as fusion partners for facile purification and are also overexpressed in certain tumors. Consequently, there is a need for sensitive detection of the enzymes. Here we describe a general strategy for the synthesis and characterization of novel fluorogenic substrates for GSTs. The substrates were synthesized by introducing an electrophilic sulfonamide linkage to fluorescent molecules containing an amino group [e.g., 2,4-dinitrobenzenesulfonamide (DNs) derivatives of coumarin, cresyl violet, and rhodamine]. The derivatives were essentially nonfluorescent, and upon GST catalyzed cleavage of the dinitrobenzenesulfonamide, free fluorophore is released (and 1-glutathionyl-2,4-dinitrobenzene + SO(2)). All the coumarin-, cresyl violet- and rhodamine-based fluorogenic probes turned out to be good substrates for most GSTs, especially for GSTA(1-1), in terms of strong fluorescence increases (71-1200-fold), high k(cat)/K(m) values (10(4)-10(7) M(-1) s(-1)) and significant rate enhancements (10(6)-10(9)-fold). The substrates were successfully applied to quantitate very low levels of GST activity in cell extracts and DNs-cresyl violet was also successfully applied to the imaging of microsomal MGST(1) activity in living cells. The cresyl violet stained cells retained their fluorescence after fixation, which is a very useful property. In summary, we describe a general and versatile strategy to generate fluorogenic GST substrates, some of them providing the most sensitive assays so far described for GSTs.

  DOI：

  10.1021/ja205500y

文献信息

• Synthesis and Characterization of a Series of Highly Fluorogenic Substrates for Glutathione Transferases, a General Strategy
  作者：Jie Zhang、Aya Shibata、Mika Ito、Satoshi Shuto、Yoshihiro Ito、Bengt Mannervik、Hiroshi Abe、Ralf Morgenstern

  DOI：10.1021/ja205500y

  日期：2011.9.7

  Glutathione transferases (GSTs) are used in biotechnology applications as fusion partners for facile purification and are also overexpressed in certain tumors. Consequently, there is a need for sensitive detection of the enzymes. Here we describe a general strategy for the synthesis and characterization of novel fluorogenic substrates for GSTs. The substrates were synthesized by introducing an electrophilic sulfonamide linkage to fluorescent molecules containing an amino group [e.g., 2,4-dinitrobenzenesulfonamide (DNs) derivatives of coumarin, cresyl violet, and rhodamine]. The derivatives were essentially nonfluorescent, and upon GST catalyzed cleavage of the dinitrobenzenesulfonamide, free fluorophore is released (and 1-glutathionyl-2,4-dinitrobenzene + SO(2)). All the coumarin-, cresyl violet- and rhodamine-based fluorogenic probes turned out to be good substrates for most GSTs, especially for GSTA(1-1), in terms of strong fluorescence increases (71-1200-fold), high k(cat)/K(m) values (10(4)-10(7) M(-1) s(-1)) and significant rate enhancements (10(6)-10(9)-fold). The substrates were successfully applied to quantitate very low levels of GST activity in cell extracts and DNs-cresyl violet was also successfully applied to the imaging of microsomal MGST(1) activity in living cells. The cresyl violet stained cells retained their fluorescence after fixation, which is a very useful property. In summary, we describe a general and versatile strategy to generate fluorogenic GST substrates, some of them providing the most sensitive assays so far described for GSTs.