[6-(2-{2-[2-(2-tert-butoxycarbonylaminoacetylamino)acetylamino]acetylamino}acetylamino)hexyl]carbamic acid tert-butyl ester | 1414960-48-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [6-(2-{2-[2-(2-tert-butoxycarbonylaminoacetylamino)acetylamino]acetylamino}acetylamino)hexyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[6-[[2-[[2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]hexyl]carbamate
• CAS: 1414960-48-7
• 化学式: C₂₄H₄₄N₆O₈
• 分子量: 544.649
• InChiKey: XZCBFQMFFDMQGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  38
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  193
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [6-(2-{2-[2-(2-tert-butoxycarbonylaminoacetylamino)acetylamino]acetylamino}acetylamino)hexyl]carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Advanced Aqueous-Phase Phosphoramidation Reactions for Effectively Synthesizing Peptide–Oligonucleotide Conjugates Trafficked into a Human Cell Line

  摘要：

  Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat(48-57) peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.

  DOI：

  10.1021/bc300444y
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 [6-(2-{2-[2-(2-tert-butoxycarbonylaminoacetylamino)acetylamino]acetylamino}acetylamino)hexyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Advanced Aqueous-Phase Phosphoramidation Reactions for Effectively Synthesizing Peptide–Oligonucleotide Conjugates Trafficked into a Human Cell Line

  摘要：

  Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat(48-57) peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.

  DOI：

  10.1021/bc300444y