3,4,6-tri-O-acetyl-2-deoxy-5-fluoro-2-phthalimido-β-D-glucosyl fluoride | 1003921-91-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3,4,6-tri-O-acetyl-2-deoxy-5-fluoro-2-phthalimido-β-D-glucosyl fluoride
• CAS: 1003921-91-2
• 化学式: C₂₀H₁₉F₂NO₉
• 分子量: 455.369
• InChiKey: YXHWPMUIKMZHCN-ISIBIEBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.07
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  125.51
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3,4,6-tri-O-acetyl-2-deoxy-5-fluoro-2-phthalimido-β-D-glucosyl fluoride 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 (2S,3S,4R,5R,6S)-5-amino-2,6-difluoro-2-(hydroxymethyl)oxane-3,4-diol
  参考文献：
  名称：

  Synthesis and Use of Mechanism-Based Protein-Profiling Probes for Retaining β-d-Glucosaminidases Facilitate Identification of Pseudomonas aeruginosa NagZ

  摘要：

  The NagZ class of retaining exo-glucosaminidases play a critical role in pepticloglycan recycling in Gram-negative bacteria and the induction of resistance to beta-lactams. Here we describe the concise synthesis of 2-azidoacetyl-2-deoxy-5-fluoro-beta-D-glucopyranosyl fluoride as an activity-based proteomics probe for profiling these exo-glycosidases. This active-site directed reagent covalently inactivates this class of retaining N-acetylglucosaminidases with exquisite selectivity by stabilizing the glycosyl-enzyme intermediate. Inactivated Vibrio cholerae NagZ can be elaborated with biotin or a FLAG-peptide epitope using the Staudinger ligation or the Sharpless-Meldal click reaction and detected at nanogram levels. This ABPP enabled the profiling of the Pseudomonas aeruginosa proteome and identification at endogenous levels of a tagged protein with properties consistent with those of PA3005. Cloning of the gene encoding this hypothetical protein and biochemical characterization enabled unambiguous assignment of this hypothetical protein as a NagZ. The identification and cloning of this NagZ may facilitate the development of strategies to circumvent resistance to beta-lactams in this human pathogen. As well, this general strategy, involving such 5-fluoro inactivators, may prove to be of general use for profiling proteomes and identifying glycoside hydrolases of medical importance or having desirable properties for biotechnology.

  DOI：

  10.1021/ja0763605
• 作为产物：
  描述：

  在 silver tetrafluoroborate 作用下， 以 乙醚 为溶剂， 反应 0.3h， 以50 mg的产率得到3,4,6-tri-O-acetyl-2-deoxy-5-fluoro-2-phthalimido-β-D-glucosyl fluoride
  参考文献：
  名称：

  Synthesis and Use of Mechanism-Based Protein-Profiling Probes for Retaining β-d-Glucosaminidases Facilitate Identification of Pseudomonas aeruginosa NagZ

  摘要：

  The NagZ class of retaining exo-glucosaminidases play a critical role in pepticloglycan recycling in Gram-negative bacteria and the induction of resistance to beta-lactams. Here we describe the concise synthesis of 2-azidoacetyl-2-deoxy-5-fluoro-beta-D-glucopyranosyl fluoride as an activity-based proteomics probe for profiling these exo-glycosidases. This active-site directed reagent covalently inactivates this class of retaining N-acetylglucosaminidases with exquisite selectivity by stabilizing the glycosyl-enzyme intermediate. Inactivated Vibrio cholerae NagZ can be elaborated with biotin or a FLAG-peptide epitope using the Staudinger ligation or the Sharpless-Meldal click reaction and detected at nanogram levels. This ABPP enabled the profiling of the Pseudomonas aeruginosa proteome and identification at endogenous levels of a tagged protein with properties consistent with those of PA3005. Cloning of the gene encoding this hypothetical protein and biochemical characterization enabled unambiguous assignment of this hypothetical protein as a NagZ. The identification and cloning of this NagZ may facilitate the development of strategies to circumvent resistance to beta-lactams in this human pathogen. As well, this general strategy, involving such 5-fluoro inactivators, may prove to be of general use for profiling proteomes and identifying glycoside hydrolases of medical importance or having desirable properties for biotechnology.

  DOI：

  10.1021/ja0763605