1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-[2-[4-[[3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]methyl]triazol-1-yl]ethyl]-5-methylpyrimidine-2,4-dione | 1012306-31-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-[2-[4-[[3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]methyl]triazol-1-yl]ethyl]-5-methylpyrimidine-2,4-dione
• CAS: 1012306-31-8
• 化学式: C₂₅H₃₃N₇O₁₀
• 分子量: 591.578
• InChiKey: IZLLSHWXEYHRNT-FLNLFJTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  211
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1-[2-deoxy-β-D-ribofuranosyl]-3-(2-azidoethyl)thymine 、 N-(3-propargyl)thymidine 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 为溶剂， 反应 8.0h， 以78%的产率得到1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-[2-[4-[[3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]methyl]triazol-1-yl]ethyl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Triazole-Linked Dumbbell Oligodeoxynucleotides with NF-κB Binding Ability as Potential Decoy Molecules

  摘要：

  [Graphics]Triazole-cross-linked oligodeoxynucleotides were synthesized with use of the Cu(I) catalyzed alkyne-azide cycloaddition (CuAAC) with oligodeoxynucleotides possessing N-3-(azidoethyl)thymidine and N-3-(propargyl)thymidine at the 3'- and 5'-termini. The newly synthesized oligodeoxynucleotides were thermally stable and their global structures retained those of non-cross-linked oligodeoxynucleotides. The newly synthesized dumbbell oligodeoxynucleotides showed excellent stability against snake venom phosphodiesterase (3'-exonuclease) and high thermal stability, which are necessary for decoy molecules to achieve biological responses leading to alteration of gene expression. Moreover; dumbbell oligodeoxynucleotides have the ability to bind to NF-kappa B p50 homodimer within a similar range to that of a control double-stranded decoy olicodeoxynucleotide. This strategy allows us to prepare triazole-linked dumbbell oligodeoxynucleotides with a range of loop lengths, and we found that the greater the number of the thymidine residues constituting the loop region, the higher the binding affinity of the dumbbell oligodeoxynucleotides to the nuclear factor kappa B. This means that a protein binding ability of the dumbbell oligodeoxynucleotides could be modulated by altering the loop size. This study clearly shows that cross-linking by the triazole Structure does not prevent the dumbbell oligodeoxynucleotides from binding to the nuclear factor kappa B transcription factor. Therefore, the results obtained conclusively demonstrate that the triazole cross-linked dumbbell oligodeoxynucleotides could be proposed as powerful decoy molecules.

  DOI：

  10.1021/jo702459b

文献信息

• Triazole-Linked Dumbbell Oligodeoxynucleotides with NF-κB Binding Ability as Potential Decoy Molecules
  作者：Masanori Nakane、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1021/jo702459b

  日期：2008.3.1

  [Graphics]Triazole-cross-linked oligodeoxynucleotides were synthesized with use of the Cu(I) catalyzed alkyne-azide cycloaddition (CuAAC) with oligodeoxynucleotides possessing N-3-(azidoethyl)thymidine and N-3-(propargyl)thymidine at the 3'- and 5'-termini. The newly synthesized oligodeoxynucleotides were thermally stable and their global structures retained those of non-cross-linked oligodeoxynucleotides. The newly synthesized dumbbell oligodeoxynucleotides showed excellent stability against snake venom phosphodiesterase (3'-exonuclease) and high thermal stability, which are necessary for decoy molecules to achieve biological responses leading to alteration of gene expression. Moreover; dumbbell oligodeoxynucleotides have the ability to bind to NF-kappa B p50 homodimer within a similar range to that of a control double-stranded decoy olicodeoxynucleotide. This strategy allows us to prepare triazole-linked dumbbell oligodeoxynucleotides with a range of loop lengths, and we found that the greater the number of the thymidine residues constituting the loop region, the higher the binding affinity of the dumbbell oligodeoxynucleotides to the nuclear factor kappa B. This means that a protein binding ability of the dumbbell oligodeoxynucleotides could be modulated by altering the loop size. This study clearly shows that cross-linking by the triazole Structure does not prevent the dumbbell oligodeoxynucleotides from binding to the nuclear factor kappa B transcription factor. Therefore, the results obtained conclusively demonstrate that the triazole cross-linked dumbbell oligodeoxynucleotides could be proposed as powerful decoy molecules.