2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide | 299931-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide
• 英文别名: 2-[2-[2-(2-tertbutoxylcarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide；2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirine-3-yl]benzylbromide；tert-butyl N-[2-[2-[2-[2-(bromomethyl)-5-[3-(trifluoromethyl)diazirin-3-yl]phenoxy]ethoxy]ethoxy]ethyl]carbamate
• CAS: 299931-15-0
• 化学式: C₂₀H₂₇BrF₃N₃O₅
• 分子量: 526.351
• InChiKey: GJDUKIHRRNJZEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  90.7
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide 在 盐酸羟胺 、 2-叔丁基亚氨基-2-二乙基氨基-1,3-二甲基全氢-1,3,2-二氮杂磷 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 (2S,4S,5R)-1-(anthracen-9-ylmethyl)-5-ethenyl-2-[(R)-(prop-2-en-1-yloxy)(quinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-1-ium bromide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-palmitoyl-3-[2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenyl]-L-alanine tert-butyl ester
  参考文献：
  名称：

  Identification of a Substrate-binding Site in a Peroxisomal β-Oxidation Enzyme by Photoaffinity Labeling with a Novel Palmitoyl Derivative

  摘要：

  Peroxisomes play an essential role in a number of important metabolic pathways including beta-oxidation of fatty acids and their derivatives. Therefore, peroxisomes possess various beta-oxidation enzymes and specialized fatty acid transport systems. However, the molecular mechanisms of these proteins, especially in terms of substrate binding, are still unknown. In this study, to identify the substrate-binding sites of these proteins, we synthesized a photoreactive palmitic acid analogue bearing a diazirine moiety as a photophore, and performed photoaffinity labeling of purified rat liver peroxisomes. As a result, an 80-kDa peroxisomal protein was specifically labeled by the photoaffinity ligand, and the labeling efficiency competitively decreased in the presence of palmitoyl-CoA. Mass spectrometric analysis identified the 80-kDa protein as peroxisomal multifunctional enzyme type 2 (MFE2), one of the peroxisomal beta-oxidation enzymes. Recombinant rat MFE2 was also labeled by the photoaffinity ligand, and mass spectrometric analysis revealed that a fragment of rat MFE2 (residues Trp(249) to Arg(251)) was labeled by the ligand. MFE2 mutants bearing these residues, MFE2(W249A) and MFE2(R251A), exhibited decreased labeling efficiency. Furthermore, MFE2(W249G), which corresponds to one of the disease-causing mutations in human MFE2, also exhibited a decreased efficiency. Based on the crystal structure of rat MFE2, these residues are located on the top of a hydrophobic cavity leading to an active site of MFE2. These data suggest that MFE2 anchors its substrate around the region from Trp(249) to Arg(251) and positions the substrate along the hydrophobic cavity in the proper direction toward the catalytic center.

  DOI：

  10.1074/jbc.m110.104547
• 作为产物：
  描述：

  2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl] benzaldehyde 在 sodium tetrahydroborate 、 四溴化碳 、 potassium carbonate 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-[2-[2-(2-tert-butoxycarbonylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide
  参考文献：
  名称：

  One-Step Synthesis of Biotinyl Photoprobes from Unprotected Carbohydrates

  摘要：

  A simple and versatile approach for the preparation of carbohydrate photoprobes has been developed. By a single-step reaction at 37 degrees C, a biotinylated carbene-generating unit was introduced to the reducing end of unprotected carbohydrates. Micromole quantities of N-acetyllactosamine, Lewis X trisaccharide, and sialyl Lewis X tetrasaccharide were easily converted to their biotinylated photoreactive analogues, which enabled the nonradioisotopic chemiluminescent detection of the photolabeled products. Thus, a sequence of lectin photoaffinity labeling, from the probe synthesis to the detection of labeled protein, was readily accomplished within one week. Our strategy may be applicable to any aldehyde-bearing ligand.

  DOI：

  10.1021/jo000414a

文献信息

• Phenyldiazirine compounds and photoaffinity labeling reagent
  申请人：Hatanaka Yasumaru

  公开号：US06903223B1

  公开（公告）日：2005-06-07

  This invention offers a photoreactive labeling reagent consisting of a novel biotinylated phenyldiazirine compound; a photoaffinity labeling reagent consisting of a saccharide-linked biotinylated phenyldiazirine compound where a saccharide compound is introduced into the novel compound; and a novel diazirine compound for such a reagent. The invention covers a biotinylated phenyldiazirine compound of the following formula (II); a phenyldiazirine compound which is an intermediate for synthesizing the above; a saccharide-linked biotinylated phenyldiazirine compound derived from the compound of the formula (II) and a saccharide compound and a method for manufacturing the same; a photoreactive labeling reagent containing the compound of the formula (II); a photoaffinity labeling reagent containing the saccharide-linked biotinylated phenyldiazirine compound; and a method for labeling a saccharide receptor using the reagent.

  这项发明提供了一种光反应性标记试剂，包括一种新型生物素化苯基重氮化合物；一种光亲和标记试剂，包括一种糖链连接的生物素化苯基重氮化合物，其中将糖类化合物引入到该新型化合物中；以及用于该试剂的一种新型重氮化合物。该发明涵盖以下化学式（II）的生物素化苯基重氮化合物；一种用于合成上述化合物的中间体苯基重氮化合物；从化学式（II）的化合物和糖类化合物衍生的糖链连接的生物素化苯基重氮化合物及其制造方法；包含化学式（II）的化合物的光反应性标记试剂；包含糖链连接的生物素化苯基重氮化合物的光亲和标记试剂；以及使用该试剂标记糖类受体的方法。
• US6903223B1
  申请人：——

  公开号：US6903223B1

  公开（公告）日：2005-06-07
• One-Step Synthesis of Biotinyl Photoprobes from Unprotected Carbohydrates
  作者：Yasumaru Hatanaka、Uwe Kempin、Park Jong-Jip

  DOI：10.1021/jo000414a

  日期：2000.9.1

  A simple and versatile approach for the preparation of carbohydrate photoprobes has been developed. By a single-step reaction at 37 degrees C, a biotinylated carbene-generating unit was introduced to the reducing end of unprotected carbohydrates. Micromole quantities of N-acetyllactosamine, Lewis X trisaccharide, and sialyl Lewis X tetrasaccharide were easily converted to their biotinylated photoreactive analogues, which enabled the nonradioisotopic chemiluminescent detection of the photolabeled products. Thus, a sequence of lectin photoaffinity labeling, from the probe synthesis to the detection of labeled protein, was readily accomplished within one week. Our strategy may be applicable to any aldehyde-bearing ligand.
• Identification of a Substrate-binding Site in a Peroxisomal β-Oxidation Enzyme by Photoaffinity Labeling with a Novel Palmitoyl Derivative
  作者：Yoshinori Kashiwayama、Takenori Tomohiro、Kotomi Narita、Miyuki Suzumura、Tuomo Glumoff、J. Kalervo Hiltunen、Paul P. Van Veldhoven、Yasumaru Hatanaka、Tsuneo Imanaka

  DOI：10.1074/jbc.m110.104547

  日期：2010.8

  Peroxisomes play an essential role in a number of important metabolic pathways including beta-oxidation of fatty acids and their derivatives. Therefore, peroxisomes possess various beta-oxidation enzymes and specialized fatty acid transport systems. However, the molecular mechanisms of these proteins, especially in terms of substrate binding, are still unknown. In this study, to identify the substrate-binding sites of these proteins, we synthesized a photoreactive palmitic acid analogue bearing a diazirine moiety as a photophore, and performed photoaffinity labeling of purified rat liver peroxisomes. As a result, an 80-kDa peroxisomal protein was specifically labeled by the photoaffinity ligand, and the labeling efficiency competitively decreased in the presence of palmitoyl-CoA. Mass spectrometric analysis identified the 80-kDa protein as peroxisomal multifunctional enzyme type 2 (MFE2), one of the peroxisomal beta-oxidation enzymes. Recombinant rat MFE2 was also labeled by the photoaffinity ligand, and mass spectrometric analysis revealed that a fragment of rat MFE2 (residues Trp(249) to Arg(251)) was labeled by the ligand. MFE2 mutants bearing these residues, MFE2(W249A) and MFE2(R251A), exhibited decreased labeling efficiency. Furthermore, MFE2(W249G), which corresponds to one of the disease-causing mutations in human MFE2, also exhibited a decreased efficiency. Based on the crystal structure of rat MFE2, these residues are located on the top of a hydrophobic cavity leading to an active site of MFE2. These data suggest that MFE2 anchors its substrate around the region from Trp(249) to Arg(251) and positions the substrate along the hydrophobic cavity in the proper direction toward the catalytic center.