2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2',3'-O-isopropylidene-5'-O-(sulfamoyl)adenosine | 1333880-67-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2',3'-O-isopropylidene-5'-O-(sulfamoyl)adenosine
• CAS: 1333880-67-3
• 化学式: C₂₇H₄₁N₇O₁₁S
• 分子量: 671.729
• InChiKey: KYZZTZVXAKOAAD-FGSUIDRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.03
• 重原子数：
  46.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  232.72
• 氢给体数：
  3.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  1-(十四碳酰氧基)-2,5-吡咯烷二酮 、 2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2',3'-O-isopropylidene-5'-O-(sulfamoyl)adenosine 、 三乙胺 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲醇 、 乙酸乙酯 为溶剂， 反应 16.0h， 以77%的产率得到2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)-prop-1-ynyl]-2',3'-O-isopropylidene-5'-O-[N-(n-tetradecanoyl)sulfamoyl]adenosine triethylammonium salt
  参考文献：
  名称：

  A high-throughput screening fluorescence polarization assay for fatty acid adenylating enzymes in Mycobacterium tuberculosis

  摘要：

  Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), encodes for an astonishing 34 fatty acid adenylating enzymes (FadDs), which play key roles in lipid metabolism. FadDs involved in lipid biosynthesis are functionally nonredundant and serve to link fatty acid and polyketide synthesis to produce some of the most architecturally complex natural lipids including the essential mycolic acids as well as the virulence-conferring phthiocerol dimycocerosates, phenolic glycolipids, and mycobactins. Here we describe the systematic development and optimization of a fluorescence polarization assay to identify small molecule inhibitors as potential antitubercular agents. We fluorescently labeled a bisubstrate inhibitor to generate a fluorescent probe/tracer, which bound with a K(D) of 245 nM to FadD28. Next, we evaluated assay performance by competitive binding experiments with a series of known ligands and assessed the impact of control parameters including incubation time, stability of the signal, temperature, and DMSO concentration. As a final level of validation the LOPAC1280 library was screened in a 384-well plate format and the assay performed with a Z-factor of 0.75, demonstrating its readiness for high-throughput screening. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.ab.2011.06.037
• 作为产物：
  描述：

  2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2',3'-O-isopropylideneadenosine 在 sodium hydride 、 氨基磺酰氯 作用下， 以 乙二醇二甲醚 、 mineral oil 为溶剂， 反应 1.5h， 以62%的产率得到2-[3-(2-{2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2',3'-O-isopropylidene-5'-O-(sulfamoyl)adenosine
  参考文献：
  名称：

  A high-throughput screening fluorescence polarization assay for fatty acid adenylating enzymes in Mycobacterium tuberculosis

  摘要：

  Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), encodes for an astonishing 34 fatty acid adenylating enzymes (FadDs), which play key roles in lipid metabolism. FadDs involved in lipid biosynthesis are functionally nonredundant and serve to link fatty acid and polyketide synthesis to produce some of the most architecturally complex natural lipids including the essential mycolic acids as well as the virulence-conferring phthiocerol dimycocerosates, phenolic glycolipids, and mycobactins. Here we describe the systematic development and optimization of a fluorescence polarization assay to identify small molecule inhibitors as potential antitubercular agents. We fluorescently labeled a bisubstrate inhibitor to generate a fluorescent probe/tracer, which bound with a K(D) of 245 nM to FadD28. Next, we evaluated assay performance by competitive binding experiments with a series of known ligands and assessed the impact of control parameters including incubation time, stability of the signal, temperature, and DMSO concentration. As a final level of validation the LOPAC1280 library was screened in a 384-well plate format and the assay performed with a Z-factor of 0.75, demonstrating its readiness for high-throughput screening. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.ab.2011.06.037