2-(bis(4-methoxyphenyl)(phenyl)methoxy)acetic acid cyanomethyl ester | 941579-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-(bis(4-methoxyphenyl)(phenyl)methoxy)acetic acid cyanomethyl ester
• 英文别名: cyanomethyl 2-(bis(4-methoxyphenyl)(phenyl)methoxy)acetate；Cyanomethyl 2-[bis(4-methoxyphenyl)-phenylmethoxy]acetate
• CAS: 941579-02-8
• 化学式: C₂₅H₂₃NO₅
• 分子量: 417.461
• InChiKey: MYDXTAALKGYDQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  77.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(bis(4-methoxyphenyl)(phenyl)methoxy)acetic acid cyanomethyl ester 、 alkaline earth salt of/the/ methylsulfuric acid 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Unexpected Preference of the E. coli Translation System for the Ester Bond during Incorporation of Backbone-Elongated Substrates

  摘要：

  There have been recent advances in the ribosomal synthesis of various molecules composed of nonnatural ribosomal substrates. However, the ribosome has strict limitations on substrates with elongated backbones. Here, we show an unexpected loophole in the E. coli translation system, based on a remarkable disparity in its selectivity for beta-amino/hydroxy acids. We challenged beta-hydroxypropionic acid (beta-HPA), which is less nucleophilic than beta-amino acids but free from protonation, to produce a new repertoire of ribosome-compatible but main-chain-elongated substrates. PAGE analysis and mass-coupled S-tag assays of amber suppression experiments using yeast suppressor tRNA(CUA)(Phe) confirmed the actual incorporation of beta-HPA into proteins/oligopeptides. We investigated the side-chain effects of beta-HPA and found that the side chain at position alpha and R stereochemistry of the beta-substrate is preferred and even notably enhances the efficiency of incorporation as compared to the parent substrate. These results indicate that the E. coli translation machinery can utilize main-chain-elongated substrates if the pK(a) of the substrate is appropriately chosen.

  DOI：

  10.1021/ja068033n
• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 在 吡啶 、 三乙胺 作用下， 反应 24.0h， 生成 2-(bis(4-methoxyphenyl)(phenyl)methoxy)acetic acid cyanomethyl ester
  参考文献：
  名称：

  Unexpected Preference of the E. coli Translation System for the Ester Bond during Incorporation of Backbone-Elongated Substrates

  摘要：

  There have been recent advances in the ribosomal synthesis of various molecules composed of nonnatural ribosomal substrates. However, the ribosome has strict limitations on substrates with elongated backbones. Here, we show an unexpected loophole in the E. coli translation system, based on a remarkable disparity in its selectivity for beta-amino/hydroxy acids. We challenged beta-hydroxypropionic acid (beta-HPA), which is less nucleophilic than beta-amino acids but free from protonation, to produce a new repertoire of ribosome-compatible but main-chain-elongated substrates. PAGE analysis and mass-coupled S-tag assays of amber suppression experiments using yeast suppressor tRNA(CUA)(Phe) confirmed the actual incorporation of beta-HPA into proteins/oligopeptides. We investigated the side-chain effects of beta-HPA and found that the side chain at position alpha and R stereochemistry of the beta-substrate is preferred and even notably enhances the efficiency of incorporation as compared to the parent substrate. These results indicate that the E. coli translation machinery can utilize main-chain-elongated substrates if the pK(a) of the substrate is appropriately chosen.

  DOI：

  10.1021/ja068033n

文献信息

• PRODUCTION METHOD FOR NONCYCLIC PEPTIDE-NUCLEIC ACID COMPLEX HAVING, AT N-TERMINAL, AMINO ACID WITH THIOL GROUP NEAR AMINO GROUP, LIBRARY THEREOF, AND CYCLIC PEPTIDE-NUCLEIC ACID COMPLEX LIBRARY DERIVED FROM SAME
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP3424941A1

  公开（公告）日：2019-01-09

  When the initiation suppression method was used for translation of a peptide having at its N terminus an amino acid residue carrying a thiol group near its amino group with specific protecting groups being introduced to the thiol group and the amino group, it was found that not only the probability of initiation of amino acid translation reaction was improved, but also production of cleaved peptides was suppressed and translation efficiency and purity were improved. Furthermore, it was found that it is possible to efficiently promote the cyclization reaction of the peptide through amide bond formation. Based on these findings, the inventors discovered novel methods for preparing complexes between nucleic acids and peptides containing various unnatural amino acids and having an amide bond-mediated cyclized portion.

  当使用起始抑制法翻译 N 端在氨基附近带有硫醇基的氨基酸残基并在硫醇基和氨基上引入特定保护基团的多肽时，发现不仅提高了氨基酸翻译反应的起始概率，而且抑制了裂解肽的产生，提高了翻译效率和纯度。此外，还发现可以通过酰胺键的形成有效促进肽的环化反应。基于这些发现，发明人发现了制备核酸与含有各种非天然氨基酸并具有酰胺键介导的环化部分的肽之间的复合物的新方法。