2-(2-{bis-[2-(1H-benzimidazol-2-ylamino)ethyl]amino}ethylamino)-3H-benzimidazole-5-carboxylic acid methyl ester | 848555-97-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(2-{bis-[2-(1H-benzimidazol-2-ylamino)ethyl]amino}ethylamino)-3H-benzimidazole-5-carboxylic acid methyl ester
• CAS: 848555-97-5
• 化学式: C₂₉H₃₂N₁₀O₂
• 分子量: 552.639
• InChiKey: PDEXCRZJKWVSDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  41.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  151.67
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-(2-{bis-[2-(1H-benzimidazol-2-ylamino)ethyl]amino}ethylamino)-3H-benzimidazole-5-carboxylic acid methyl ester 在 盐酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Site-Specific Cleavage of RNA by a Metal-Free Artificial Nuclease Attached to Antisense Oligonucleotides

  摘要：

  RNA cleaving tris(2-aminobenzimidazoles) have been attached to DNA oligonucleotides via disulfide or amide bonds. The resulting conjugates are effective organocatalytic nucleases showing substrate and site selectivity as well as saturation kinetics. The benzimidazole conjugates also degrade enantiomeric RNA. This observation rules out contamination effects as an alternative explanation of RNA degradation. The pH dependency shows that the catalyst is most active in the deprotonated state. Typical half-lifes of RNA substrates are in the range of 12-17 h. Thus, conjugates of tris(2-aminobenzimidazoles) can compete with the majority of metal-dependent artificial nucleases.

  DOI：

  10.1021/ja061036f
• 作为产物：
  描述：

  三(2-氨基乙基)胺 在 palladium on activated charcoal 咪唑 、 氯化亚砜 、 氨 、 氢气 、 sulfur 、 三乙胺 、 mercury(II) oxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 60.0 ℃ 、5.0 MPa 条件下， 反应 17.0h， 生成 2-(2-{bis-[2-(1H-benzimidazol-2-ylamino)ethyl]amino}ethylamino)-3H-benzimidazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Metal-Free Catalysts for the Hydrolysis of RNA Derived from Guanidines, 2-Aminopyridines, and 2-Aminobenzimidazoles

  摘要：

  2-Aminopyridine and 2-aminobenzimidazole were chosen as structural analogues to substitute guanidinium groups in receptor molecules designed as phosphoryl transfer catalysts. Shifting the pK(a) of the guanidinium analogues toward 7 was expected to raise catalytic activities in aqueous buffer. Although the pK(a)'s of both heterocycles are similar (6.2 and 7.0), only 2-aminobenzimidazole led to active RNA cleavers. All cleavage assays were run with fluorescently labeled substrates and a DNA sequencer. RNase contaminations would degrade RNA enantioselectively. In contrast, achiral catalysts such as 9b and 10b necessarily induce identical cleavage patterns in RNA and its mirror image. This principle allowed us to safely rule out contamination effects in this study. The most active catalysts, tris(2-aminobenzimidazoles) 9b and 1 Ob, were shown by fluorescence correlation spectroscopy (FCS) to aggregate with oligonucleotides. However, at very low concentrations the compounds are still active in the nonaggregated state. Conjugates of 10b with antisense oligonucleotides or RNA binding peptides, therefore, will be promising candidates as site specific artificial ribonucleases.

  DOI：

  10.1021/ja0443934

文献信息

• Site-Specific Cleavage of RNAs Derived from the PIM1 3′-UTR by a Metal-Free Artificial Ribonuclease
  作者：Felix Zellmann、Laura Thomas、Ute Scheffer、Roland Hartmann、Michael Göbel

  DOI：10.3390/molecules24040807

  日期：——

  increased the cleavage rate. Tris(2-aminobenzimidazoles) were designed to interact with phosphates and phosphate esters. A cell, however, contains large amounts of phosphorylated species that may cause competitive inhibition of RNA cleavage. It is thus important to note that no loss in reaction rates was observed in phosphate buffer. This opens the way to in-cell applications for this type of artificial nuclease

  先前已经报道了三（2-氨基苯并咪唑）的寡核苷酸缀合物以高水平的序列和位点特异性切割互补的RNA链。这些研究中使用的RNA底物是不超过29个单体的寡核苷酸。在这里，我们显示来自PIM1 mRNA 3'-非翻译区的〜150-400-mer模型转录物以与短寡核苷酸底物相当的速率和特异性反应。用DNA / LNA混合器替代DNA进一步提高了切割速率。Tris（2-氨基苯并咪唑）被设计为与磷酸盐和磷酸酯相互作用。但是，细胞中含有大量的磷酸化物质，可能导致竞争性抑制RNA切割。因此，重要的是要注意在磷酸盐缓冲液中未观察到反应速率的损失。这为这种类型的人工核酸酶在细胞内应用开辟了道路。此外，我们公开了一种新的合成方法，可以以克数访问三（2-氨基苯并咪唑）。
• A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates
  作者：Felix Zellmann、Michael W. Göbel

  DOI：10.3390/molecules25081842

  日期：——

  low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts

  当连接到寡核苷酸的 5' 末端时，RNA 切割催化剂三（2-氨基苯并咪唑）以高度位点特异性的方式切割互补的 RNA 链。先前通过使用催化剂的活性酯酰化氨基接头来实现缀合。然而，该程序产量低且不可靠。在这里，描述了一种亚磷酰胺结构单元，它可以通过手动固相合成与寡核苷酸偶联，总产率约为 85%。基于这种化学反应，我们现在研究了 LNA（锁核酸）核苷酸对 RNA 裂解偶联物的速率和位点特异性的影响。当催化剂连接到强大的 5' 闭合碱基对上并且寡核苷酸包含几个均匀分布在链中的 LNA 单元时，可以预期最高的反应速率和最精确的切割。然而，当放置在 5' 位置时，LNA 构建模块往往会降低 RNA 切割的特异性。
• Quality Control of mRNA Vaccines by Synthetic Ribonucleases: Analysis of the Poly‐A‐Tail
  作者：Felix Zellmann、Nina Schmauk、Nina Murmann、Madeleine Böhm、Alexander Schwenger、Michael W. Göbel

  DOI：10.1002/cbic.202400347

  日期：2024.7.2

  The effectivity and safety of mRNA vaccines critically depends on the presence of correct 5’ caps and poly‐A tails. Due to the high molecular mass of full‐size mRNAs, however, the direct analysis by mass spectrometry is hardly possible. Here we describe the use of synthetic ribonucleases to cleave off 5’ and 3’ terminal fragments which can be further analyzed by HPLC or by LC–MS. Compared to existing methods (e. g. RNase H), the new approach uses robust catalysts, is free of sequence limitations, avoids metal ions and combines fast sample preparation with high precision of the cut.