N²-(R)-(1-carboxyethyl)-2'-deoxyguanosine | 739343-22-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N²-(R)-(1-carboxyethyl)-2'-deoxyguanosine
• 英文别名: N(2)-(R)-carboxyethyl-2'-deoxyguanosine；(2R)-2-[[9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]amino]propanoic acid
• CAS: 739343-22-7
• 化学式: C₁₃H₁₇N₅O₆
• 分子量: 339.308
• InChiKey: MXNKUBJIXVVNPY-ULAWRXDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  158
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 溶剂黄146 作用下， 反应 1.0h， 生成 N²-(R)-(1-carboxyethyl)-2'-deoxyguanosine
  参考文献：
  名称：

  Stereospecific Synthesis and Characterization of Oligodeoxyribonucleotides Containing an N²-(1-Carboxyethyl)-2‘-deoxyguanosine

  摘要：

  Methylglyoxal is a highly reactive a-ketoaldehyde that is produced endogenously and present in the environment and foods. It can modify DNA and proteins to form advanced glycation end products (AGES). Emerging evidence has shown that N-2-(l-carboxyethyl)-2 '-deoxyguanosine (N-2-CEdG) is a major marker for AGE-linked DNA adducts. Here, we report, for the first time, the preparation of oligodeoxyribonucleotides (ODNs) containing individual diastereomers of N-2-CEdG via a postoligomerization synthesis method, which provided authentic substrates for examining the replication and repair of this lesion. In addition, thermodynamic parameters derived from melting temperature data revealed that the two diastereomers of N-2-CEdG destabilized significantly the double helix as represented by a 4 kcal/mol increase in Gibbs free energy for duplex formation at 25 degrees C. Primer extension assay results demonstrated that both diastereomers; of N-2-CEdG could block considerably the replication synthesis mediated by the exonuclease-free Klenow fragment of Escherichia coli DNA polymerase 1. Strikingly, the polymerase incorporated incorrect nucleotides, dGMP and dAMP, opposite the lesion more preferentially than the correct nucleotide, dCMP.

  DOI：

  10.1021/ja072130e