5-bromo-2'-O,4'-C-methyleneuridine | 320590-22-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-bromo-2'-O,4'-C-methyleneuridine
• 英文别名: 5-bromo-1-[(1S,3R,4R,7S)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]pyrimidine-2,4-dione
• CAS: 320590-22-5
• 化学式: C₁₀H₁₁BrN₂O₆
• 分子量: 335.111
• InChiKey: BEMFVMGZYGSFMT-RZWCQZFCSA-N

物化性质

• 密度：
  2.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-bromo-2'-O,4'-C-methyleneuridine 在 吡啶 、 4-二甲氨基吡啶 、 硫酸氢铵 、 二异丙基铵盐四氮唑 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 104.67h， 生成 1-[3'-O-[2-cyanoethoxy(diisopropylamino)phosphino]-5'-O-(4,4'-dimethoxytrityl)-2'-O,4'-C-methylene-β-D-ribofuranosyl]-5-methyl-4-(1,2,4-triazol-1-yl)pyrimidinone
  参考文献：
  名称：

  2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA)

  摘要：

  For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance. there is only limited information available on the tripler-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of tripler-forming oligonucleotide: (TFO) significantly enhances the binding affinity towards target dsDNA. On T, measurements. the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with DeltaT(m)/modification of +4.3 to + 5 degreesC at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2'.4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-K-B transcription factor (p50)-target dsDNA binding by forming a stable tripler at pH 7.0. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00325-4
• 作为产物：
  描述：

  3'-O-benzyl-2'-O,4'-C-methyleneuridine 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 氢气 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 42.0h， 生成 5-bromo-2'-O,4'-C-methyleneuridine
  参考文献：
  名称：

  2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA)

  摘要：

  For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance. there is only limited information available on the tripler-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of tripler-forming oligonucleotide: (TFO) significantly enhances the binding affinity towards target dsDNA. On T, measurements. the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with DeltaT(m)/modification of +4.3 to + 5 degreesC at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2'.4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-K-B transcription factor (p50)-target dsDNA binding by forming a stable tripler at pH 7.0. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00325-4

文献信息

• Triplex-forming enhancement with high sequence selectivity by single 2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA) modification
  作者：Satoshi Obika、Yoshiyuki Hari、Tomomi Sugimoto、Mitsuaki Sekiguchi、Takeshi Imanishi

  DOI：10.1016/s0040-4039(00)01607-5

  日期：2000.11

  Tripler-forming ability of the oligonucleotides containing one 2'-O,3'-C-methyleneribonucleic acid (2',4'-BNA) unit was investigated by measurement of the melting temperature (T-m), and the 2',4'-BNA modification promoted the marked tripler stabilization in a highly sequence-selective manner. (C) 2000 Elsevier Science Ltd. All rights reserved.
• CHEMICALLY-MODIFIED GUIDE RNAS TO IMPROVE CRISPR-CAS PROTEIN SPECIFICITY
  申请人：THE GOVERNORS OF THE UNIVERSITY OF ALBERTA

  公开号：US20210277392A1

  公开（公告）日：2021-09-09

  A method of increasing specificity of binding of a CRISPR-Cas protein-guide RNA complex to a selected target nucleic acid sequence is provided. The method comprises contacting a nucleic acid molecule comprising the selected target nucleic acid sequence with the complex comprising the CRISPR-Cas protein and the guide RNA, wherein the guide RNA comprises a complementarity region at the 5′ end of the guide RNA that binds to a complementary strand of the selected target nucleic acid sequence, wherein the guide RNA comprises at least one modified nucleic acid within the complementarity region; wherein the guide RNA complementarity region binds and directs the CRISPR-Cas protein (e.g. CRISPR/Cas9) to the selected target nucleic acid sequence, thereby increasing specificity of binding of the CRISPR-Cas protein-guide RNA complex to the selected target nucleic acid sequence. The modified nucleic acid may be a bridged nucleic acid, a deoxyribonucleic acid, or a 2-0-methyl RNA phosphonoacetate-modified crRNA, or a functional equivalent that improves specificity by inducing similar conformational changes in the CRISPR-Cas system. Guide RNAs, kits comprising a guide RNA together with a CRISPR-Cas protein, and complexes comprising a guide RNA and a CRISPR-Cas proteins are also provided.