(1S,2R,4R)-4-{[2-(acetylamino)-5-(formylamino)-6-oxo-1,6-dihydro-4-pyrimidinyl]amino}-2-{[(dimethoxytrityl)oxy]methyl}cyclopentyl-O-(N,N-diisopropyl)-(2-cyanoethyl)phosphoramidite

• 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: (1S,2R,4R)-4-{[2-(acetylamino)-5-(formylamino)-6-oxo-1,6-dihydro-4-pyrimidinyl]amino}-2-{[(dimethoxytrityl)oxy]methyl}cyclopentyl-O-(N,N-diisopropyl)-(2-cyanoethyl)phosphoramidite
• 英文别名: (1'S,2'R,4'R)-4-((2-Acetamido-5-formamido-6-oxo-1,6-dihydropyrimidin-4-yl)-amino)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)cyclopentyl(2-cyanoethyl)diisopropylphosphoramidite；N-[4-[[(1R,3R,4S)-3-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxycyclopentyl]amino]-5-formamido-6-oxo-1H-pyrimidin-2-yl]acetamide
• 化学式: C₄₃H₅₄N₇O₈P
• 分子量: 827.918
• InChiKey: DZXIMAPKLDPYQY-GWVCWUGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  59
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  185
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (+)-(1S,2R,4R)-4-氨基-2-(羟甲基)-1-环戊醇 在 palladium on activated charcoal 吡啶 、 咪唑 、 4 A molecular sieve 、 二异丙基铵盐四氮唑 、 氢气 、 氟化氢吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 75.0 ℃ 、120.0 kPa 条件下， 反应 58.0h， 生成 (1S,2R,4R)-4-{[2-(acetylamino)-5-(formylamino)-6-oxo-1,6-dihydro-4-pyrimidinyl]amino}-2-{[(dimethoxytrityl)oxy]methyl}cyclopentyl-O-(N,N-diisopropyl)-(2-cyanoethyl)phosphoramidite
  参考文献：
  名称：

  Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion

  摘要：

  The 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG) is one of the major DNA lesions found after oxidative stress in cells. To clarify the base pairing and coding potential of this major DNA lesion with the aim to estimate its mutagenic effect, we prepared oligonucleotides containing a cyclopentane based analogue of the DNA lesion (cFaPydG). In addition, oligonucleoticles containing the cyclopentane analogue of 2'-deoxyguanosine (cdG), and oligonucleotides containing 8-oxo-7,8-dihydro2'-deoxyguanosine (8-oxodG) were synthesized. The thermodynamic stability of duplexes containing these building blocks and all canonical counterbases were determined by concentration dependent melting-point measurements (van't Hoff plots). The data reveal that cFaPydG greatly destabilizes a DNA duplex (Delta Delta G(o)298K approximate to 2-4 kcal mol(-1)). The optimal base pairing partner for the cFaPydG lesion is dC. Investigation of duplexes containing dG and cdG shows that the effect of substituting the deoxyribose by a cyclopentane moiety is marginal. The data also provide strong evidence that the FaPydG lesion is unable to form a base pair with dA. Our computational studies indicate that the syn-conformation required for base pairing with dA is energetically unfavorable. This is in contrast to 8-oxodG for which the syn-conformation represents the energetic minimum. Kinetic primer extension studies using S. cerevisiae Pol eta reveal that cFaPydG is replicated in an error-free fashion. dC is inserted 2-3 orders of magnitude more efficiently than dT or CIA, showing that FaPydG is a lesion which retains the coding potential of dG. This is also in contrast to 8-oxodG, for which base pairing with dC and dA was established.

  DOI：

  10.1021/ja0549188

文献信息

• The Two Main DNA Lesions 8-Oxo-7,8-dihydroguanine and 2,6-Diamino-5-formamido-4-hydroxypyrimidine Exhibit Strongly Different Pairing Properties
  作者：Matthias Ober、Uwe Linne、Johannes Gierlich、Thomas Carell

  DOI：10.1002/anie.200351287

  日期：2003.10.20
• Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion
  作者：Matthias Ober、Heiko Müller、Carsten Pieck、Johannes Gierlich、Thomas Carell

  DOI：10.1021/ja0549188

  日期：2005.12.1

  The 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG) is one of the major DNA lesions found after oxidative stress in cells. To clarify the base pairing and coding potential of this major DNA lesion with the aim to estimate its mutagenic effect, we prepared oligonucleotides containing a cyclopentane based analogue of the DNA lesion (cFaPydG). In addition, oligonucleoticles containing the cyclopentane analogue of 2'-deoxyguanosine (cdG), and oligonucleotides containing 8-oxo-7,8-dihydro2'-deoxyguanosine (8-oxodG) were synthesized. The thermodynamic stability of duplexes containing these building blocks and all canonical counterbases were determined by concentration dependent melting-point measurements (van't Hoff plots). The data reveal that cFaPydG greatly destabilizes a DNA duplex (Delta Delta G(o)298K approximate to 2-4 kcal mol(-1)). The optimal base pairing partner for the cFaPydG lesion is dC. Investigation of duplexes containing dG and cdG shows that the effect of substituting the deoxyribose by a cyclopentane moiety is marginal. The data also provide strong evidence that the FaPydG lesion is unable to form a base pair with dA. Our computational studies indicate that the syn-conformation required for base pairing with dA is energetically unfavorable. This is in contrast to 8-oxodG for which the syn-conformation represents the energetic minimum. Kinetic primer extension studies using S. cerevisiae Pol eta reveal that cFaPydG is replicated in an error-free fashion. dC is inserted 2-3 orders of magnitude more efficiently than dT or CIA, showing that FaPydG is a lesion which retains the coding potential of dG. This is also in contrast to 8-oxodG, for which base pairing with dC and dA was established.