2,2-Dimethyl-propionic acid (2R,3S,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester | 208330-03-4

• 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: 2,2-Dimethyl-propionic acid (2R,3S,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester
• CAS: 208330-03-4
• 化学式: C₁₆H₂₄N₂O₆S
• 分子量: 372.442
• InChiKey: JHSQCTASCNCGOX-DMDPSCGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.12
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  99.62
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-propionic acid (2R,3S,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester 在 吡啶 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 4 A molecular sieve 、 氨 、 水 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 19.08h， 生成 1-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-((((2R,3S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)methoxy)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthesis, Crystal Structure, and Enzymatic Evaluation of a DNA-Photolesion Isostere

  摘要：

  Nucleotide analogues are useful tools for the investigation of interactions between DNA-binding proteins and DNA at a molecular level. Herein we describe the synthesis of the DNA-lesion analogue 2, which is required to determine the extent to which specific phosphodiesters in the DNA backbone contribute to the recognition of cyclobutane pyrimidine dimer DNA lesion by the dimer-specific repair enzymes DNA photolyases or T4-endonuclease V. The analogue 2 is a close structural mimic of cyclobutane pyrimidine dimers like 1. which are the major lesions induced upon irradiation of cells with UV light. Instead of the negatively charged phosphate link in 1, analogue 2 contains an uncharged but isosteric formacetal moiety. The analysis of this and other phosphodiester contacts is hoped to provide insight into the lesion recognition process, which is currently believed to require the nipping of the lesioned base out of the DNA double helix. The lesion analogue 2 is synthetically available in large quantities, which allowed us to establish a new, fast and sensitive DNA photolyase assay. A precise X-ray crystal structure analysis of the DNA-lesion analogue 2 is also presented. The structure underlines the isosteric character of 2 and reveals, in combination with the only other available X-ray crystal structure determined from a thymine-dimer triester analogue, interesting structural features of cyclobutane pyrimidine dimer lesions. We describe the incorporation of the lesion analogue 2 into oligonucleotides by using standard phosphoramidite chemistry. Initial enzymatic repair studies are reported with three different types of DNA photolyases. These studies show that the lesion analogue 2 is rapidly repaired by photolyases from Anacystis nidulans, Neurospora crassa and from the marsupial Potorous tridactylis. The enzymatic investigations indicate that all photolyases, including enzymes from higher organisms (Tridactylis) accept the formacetal dimer as a lesion substrate and therefore could possess a similar DNA-lesion recognition process, in which the interaction with the central phosphate unit is only of limited importance.

  DOI：

  10.1002/(sici)1521-3765(19980416)4:4<642::aid-chem642>3.0.co;2-k
• 作为产物：
  描述：

  二甲基亚砜 、 O^5'-(2,2-dimethyl-propionyl)-2'-deoxy-uridine 在 乙酸酐 作用下， 以 溶剂黄146 为溶剂， 反应 70.0h， 以58%的产率得到2,2-Dimethyl-propionic acid (2R,3S,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  Synthesis, Crystal Structure, and Enzymatic Evaluation of a DNA-Photolesion Isostere

  摘要：

  Nucleotide analogues are useful tools for the investigation of interactions between DNA-binding proteins and DNA at a molecular level. Herein we describe the synthesis of the DNA-lesion analogue 2, which is required to determine the extent to which specific phosphodiesters in the DNA backbone contribute to the recognition of cyclobutane pyrimidine dimer DNA lesion by the dimer-specific repair enzymes DNA photolyases or T4-endonuclease V. The analogue 2 is a close structural mimic of cyclobutane pyrimidine dimers like 1. which are the major lesions induced upon irradiation of cells with UV light. Instead of the negatively charged phosphate link in 1, analogue 2 contains an uncharged but isosteric formacetal moiety. The analysis of this and other phosphodiester contacts is hoped to provide insight into the lesion recognition process, which is currently believed to require the nipping of the lesioned base out of the DNA double helix. The lesion analogue 2 is synthetically available in large quantities, which allowed us to establish a new, fast and sensitive DNA photolyase assay. A precise X-ray crystal structure analysis of the DNA-lesion analogue 2 is also presented. The structure underlines the isosteric character of 2 and reveals, in combination with the only other available X-ray crystal structure determined from a thymine-dimer triester analogue, interesting structural features of cyclobutane pyrimidine dimer lesions. We describe the incorporation of the lesion analogue 2 into oligonucleotides by using standard phosphoramidite chemistry. Initial enzymatic repair studies are reported with three different types of DNA photolyases. These studies show that the lesion analogue 2 is rapidly repaired by photolyases from Anacystis nidulans, Neurospora crassa and from the marsupial Potorous tridactylis. The enzymatic investigations indicate that all photolyases, including enzymes from higher organisms (Tridactylis) accept the formacetal dimer as a lesion substrate and therefore could possess a similar DNA-lesion recognition process, in which the interaction with the central phosphate unit is only of limited importance.

  DOI：

  10.1002/(sici)1521-3765(19980416)4:4<642::aid-chem642>3.0.co;2-k