TG-mPC3C | 1253913-14-2

• 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: TG-mPC3C
• 英文别名: [9-(4-Methoxy-2-methylphenyl)-6-oxoxanthen-3-yl]oxymethyl 3-(trimethylazaniumyl)propyl phosphate
• CAS: 1253913-14-2
• 化学式: C₂₈H₃₂NO₈P
• 分子量: 541.538
• InChiKey: NRIALYUNDZZZFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  TG-mPC3C 在 recombinant pyrophosphatase/phosphodiesterase-6 作用下， 以 二甲基亚砜 为溶剂， 生成 Tokyo green
  参考文献：
  名称：

  Fluorescence Probe for Lysophospholipase C/NPP6 Activity and a Potent NPP6 Inhibitor

  摘要：

  Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC(3)C, TG-mPC(5)C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC(3)C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80 000 compounds. Through structure activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC50 value of 0.21 mu M. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6.

  DOI：

  10.1021/ja201028t
• 作为产物：
  描述：

  Dibenzyl [9-(4-methoxy-2-methylphenyl)-6-oxoxanthen-3-yl]oxymethyl phosphate 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 TG-mPC3C
  参考文献：
  名称：

  Fluorescence Probe for Lysophospholipase C/NPP6 Activity and a Potent NPP6 Inhibitor

  摘要：

  Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC(3)C, TG-mPC(5)C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC(3)C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80 000 compounds. Through structure activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC50 value of 0.21 mu M. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6.

  DOI：

  10.1021/ja201028t

文献信息

• Fluorescence Probe for Lysophospholipase C/NPP6 Activity and a Potent NPP6 Inhibitor
  作者：Mitsuyasu Kawaguchi、Takayoshi Okabe、Shinichi Okudaira、Kenjiro Hanaoka、Yuuta Fujikawa、Takuya Terai、Toru Komatsu、Hirotatsu Kojima、Junken Aoki、Tetsuo Nagano

  DOI：10.1021/ja201028t

  日期：2011.8.10

  Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC(3)C, TG-mPC(5)C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC(3)C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80 000 compounds. Through structure activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC50 value of 0.21 mu M. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6.