12-{(11-Carboxy-undecylsulfanyl)-[4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenyl]-methylsulfanyl}-dodecanoic acid | 149183-56-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 12-{(11-Carboxy-undecylsulfanyl)-[4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenyl]-methylsulfanyl}-dodecanoic acid
• CAS: 149183-56-2
• 化学式: C₃₃H₅₁F₃N₂O₄S₂
• 分子量: 660.906
• InChiKey: XXXPPWVASQXUGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  44.0
• 可旋转键数：
  28.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  99.32
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  lyso-(N-tert-butyloxy)carbonyl-myristoylphosphatidylethanolamine methyl ester 、 12-{(11-Carboxy-undecylsulfanyl)-[4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenyl]-methylsulfanyl}-dodecanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到
  参考文献：
  名称：

  Design, synthesis, and properties of a photoactivatable membrane-spanning phospholipidic probe

  摘要：

  We introduce here a new photochemical probe suitable for labeling deep into the hydrophobic core of membranes: bis-phosphatidylethanolamine (trifluoromethyl)phenyldiazirine 19 (DIPETPD). This is a bipolar phospholipid provided with a covalently bonded chain designed to span the membrane and equipped with a centrally defined attachment point for the photolabeling group (trifluoromethyl)phenyldiazirine (TPD). This molecule was designed to enhance the geometrical resolution of photochemical labeling of membrane proteins by locating the photoreactive functionality in the center of the bilayer. The remarkable chemical stability of the photoreactive group TPD1 allowed the design of a straightforward and convergent synthetic strategy. The key steps developed for molecules of this new general kind are (a) the mild and efficient coupling of two moieties of N-tBOC-protected lysophosphatidylethanolamine methyl ester to the photoreactive symmetric dicarboxylic fatty acid mediated by dicyclohexylcarbodiimide and (dimethylamino)pyridine and (b) the smooth deprotection of the phosphate and amino functionalities with sodium iodide and trifluoroacetic acid, respectively, to yield the final product. DIPETPD has been successfully incorporated into small and large unilamellar vesicles of different lipid composition and prepared by a variety of procedures. The bilayer location of this reagent (transmembrane vs 'U'-shaped conformations) was assayed by reaction of the amino groups at the polar heads of the bipolar phospholipid with selected membrane-impermeable reagents. Photolysis of the probe incorporated into vesicles occurs readily upon irradiation with UV light (near 360 nm). These 'loaded' vesicles show adequate stability and appear uniform and unilamellar in electron micrographs. They undergo the fusion reaction with influenza virus as efficiently as reagent-free vesicles. Evidence is presented here that DIPETPD and a reductively methylated form efficiently label the peptide ion channel form of gramicidin A (and a chemical analogue) and the influenza virus hemagglutinin. DIPETPD may help to identify transmembrane regions of integral membrane proteins and map the lipid-protein interface in a region known to be deep in the membrane. A new radioactive version of this reagent ([H-3]-DIPETPD)2 has been recently used to ascertain that the HA2 subunit of influenza virus hemagglutinin inserts into the target membrane prior to fusion.3

  DOI：

  10.1021/ja00062a009
• 作为产物：
  描述：

  12-((ethoxy(thiocarbonyl))thio)dodecanoic acid 在 sodium tetrahydroborate 、 三氟化硼乙醚 、 乙二胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 12-{(11-Carboxy-undecylsulfanyl)-[4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenyl]-methylsulfanyl}-dodecanoic acid
  参考文献：
  名称：

  Design, synthesis, and properties of a photoactivatable membrane-spanning phospholipidic probe

  摘要：

  We introduce here a new photochemical probe suitable for labeling deep into the hydrophobic core of membranes: bis-phosphatidylethanolamine (trifluoromethyl)phenyldiazirine 19 (DIPETPD). This is a bipolar phospholipid provided with a covalently bonded chain designed to span the membrane and equipped with a centrally defined attachment point for the photolabeling group (trifluoromethyl)phenyldiazirine (TPD). This molecule was designed to enhance the geometrical resolution of photochemical labeling of membrane proteins by locating the photoreactive functionality in the center of the bilayer. The remarkable chemical stability of the photoreactive group TPD1 allowed the design of a straightforward and convergent synthetic strategy. The key steps developed for molecules of this new general kind are (a) the mild and efficient coupling of two moieties of N-tBOC-protected lysophosphatidylethanolamine methyl ester to the photoreactive symmetric dicarboxylic fatty acid mediated by dicyclohexylcarbodiimide and (dimethylamino)pyridine and (b) the smooth deprotection of the phosphate and amino functionalities with sodium iodide and trifluoroacetic acid, respectively, to yield the final product. DIPETPD has been successfully incorporated into small and large unilamellar vesicles of different lipid composition and prepared by a variety of procedures. The bilayer location of this reagent (transmembrane vs 'U'-shaped conformations) was assayed by reaction of the amino groups at the polar heads of the bipolar phospholipid with selected membrane-impermeable reagents. Photolysis of the probe incorporated into vesicles occurs readily upon irradiation with UV light (near 360 nm). These 'loaded' vesicles show adequate stability and appear uniform and unilamellar in electron micrographs. They undergo the fusion reaction with influenza virus as efficiently as reagent-free vesicles. Evidence is presented here that DIPETPD and a reductively methylated form efficiently label the peptide ion channel form of gramicidin A (and a chemical analogue) and the influenza virus hemagglutinin. DIPETPD may help to identify transmembrane regions of integral membrane proteins and map the lipid-protein interface in a region known to be deep in the membrane. A new radioactive version of this reagent ([H-3]-DIPETPD)2 has been recently used to ascertain that the HA2 subunit of influenza virus hemagglutinin inserts into the target membrane prior to fusion.3

  DOI：

  10.1021/ja00062a009