1-(2-deoxy-β-D-erythro-pentofuranosyl)-5(R)-hydroxy-5-methylhydantoin | 38716-09-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5(R)-hydroxy-5-methylhydantoin
• 英文别名: N₁-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin；(5R)-5-Hydroxy-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl)-5-methyl-imidazolidine-2,4-dione；(5R)-5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylimidazolidine-2,4-dione
• CAS: 38716-09-5
• 化学式: C₉H₁₄N₂O₆
• 分子量: 246.22
• InChiKey: FDZJCTAGSKTDIR-BKIHBWCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]-5-methylimidazolidine-2,4-dione 在 ammonium hydroxide 、 溶剂黄146 作用下， 反应 4.5h， 生成 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5(R)-hydroxy-5-methylhydantoin
  参考文献：
  名称：

  Repair and Coding Properties of 5-Hydroxy-5-methylhydantoin Nucleosides Inserted into DNA Oligomers

  摘要：

  1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd) (3) has been shown to be a major oxidation product of thymidine formed upon exposure of DNA to (OH)-O-.-radical and excited photosensitizers. To investigate the biological and structural significance of the 6-OH-5-Me-dHyd residue to DNA, the latter modified 2'-deoxyribonucleoside was chemically prepared and then site-specifically incorporated into oligo deoxyribonucleotides. This was efficiently achieved using the phosphoramidite approach that involved mild deprotection conditions. The purity and the integrity of the modified synthetic DNA fragments were checked using different complementary techniques such as HPLC and polyacrylamide gel electrophoresis, together with electrospray ionization and MALDI-TOF mass spectrometry. The piperidine test applied to 5-OH-5-Me-dHyd containing oligonucleotides showed a weak instability of hydantoin nucleoside inserted into the oligonucleotide chain. Several enzymatic experiments aimed at determining the biochemical features of such a DNA lesion were carried out. Thus, processing of 5-OH-5-Me-dHyd by nuclease P-1, snake venom phosphodiesterase, and calf spleen phosphodiesterase was investigated. The specificity and the mechanism of excision of the lesion by several bacterial and yeast DNA N-glycosylases, namely, endonuclease III (endo III), endonuclease VIII (endo VIII), formamidopyrimidine DNA N-glycosylase (Fpg), Ntg1 protein (Ntg1), Ntg2 protein (Ntg2), and Ogg1 protein (yOgg1), were also determined. These repair studies clearly showed that all these enzymes, with the exception of the yOgg1 protein, are able to recognize and remove 5-hydroxy-5-methylhydantoin from the double-stranded DNA fragment. Finally, a 22-mer DNA oligomer bearing a 5-OH-5-Me-dHyd residue was used as a template to study the in vitro nucleotide incorporation opposite the damage by the Klenow fragment of Escherichia coli polymerase I, Taq DNA polymerase, and DNA polymerase beta. Thus, it may be concluded that the oxidized thymine residue is a strongly blocking lesion for the three studied DNA polymerases.

  DOI：

  10.1021/tx000005+

文献信息

• Isomerization of 5-Hydroxy-5-methylhydantoin 2′-Deoxynucleoside into α-Furanose, β-Furanose, α-Pyranose, and β-Pyranose Anomers
  作者：Anum Ali、J. Richard Wagner

  DOI：10.1021/acs.chemrestox.5b00406

  日期：2016.1.19

  5-hydroxyhydantoin derivatives. 5-Hydroxyhydantoin modifications are interesting because they undergo ring–chain tautomerism into a pair of diastereomers via an open chain carbonyl intermediate. Here, we show that purified diastereomers of N1-(2-deoxy-β-d-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin not only undergo isomerization into a mixture of 5R and 5S diastereomers of the hydantoin ring but also

  氧化损伤是生物产生的氧或氮反应性物种导致的最常见的DNA损伤类型之一。羟基自由基，一种电子氧化剂和各种化学氧化剂（如高锰酸盐和臭氧）与DNA，胞嘧啶和胸腺嘧啶中的嘧啶碱基反应，生成5-羟基乙内酰脲衍生物。5-羟基乙内酰脲的修饰很有趣，因为它们通过开链羰基中间体经历环链互变异构成一对非对映异构体。在这里，我们显示了N 1-（2-deoxy-β- d的纯化非对映异构体-赤型-五氟呋喃糖基）-5-羟基-5-甲基乙内酰脲不仅会异构化成乙内酰脲环的5R和5S非对映异构体的混合物，而且还会变成另外三对非对映异构体，其中糖部分转化为α-呋喃糖β -吡喃糖和α-吡喃糖异构体。通过广泛的NMR分析表征了新型5-羟基-5-甲基乙内酰脲衍生物。进一步的研究表明，与较高的pH值相比，在pH 6时异构化得到了极大的抑制。提出了一种新的异构化机制，以解释在中性pH下核苷异构体的形成，这涉及乙内酰脲和糖基团的环链互变异
• Repair and Coding Properties of 5-Hydroxy-5-methylhydantoin Nucleosides Inserted into DNA Oligomers
  作者：Didier Gasparutto、Mourad Ait-Abbas、Michel Jaquinod、Serge Boiteux、Jean Cadet

  DOI：10.1021/tx000005+

  日期：2000.7.1

  1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd) (3) has been shown to be a major oxidation product of thymidine formed upon exposure of DNA to (OH)-O-.-radical and excited photosensitizers. To investigate the biological and structural significance of the 6-OH-5-Me-dHyd residue to DNA, the latter modified 2'-deoxyribonucleoside was chemically prepared and then site-specifically incorporated into oligo deoxyribonucleotides. This was efficiently achieved using the phosphoramidite approach that involved mild deprotection conditions. The purity and the integrity of the modified synthetic DNA fragments were checked using different complementary techniques such as HPLC and polyacrylamide gel electrophoresis, together with electrospray ionization and MALDI-TOF mass spectrometry. The piperidine test applied to 5-OH-5-Me-dHyd containing oligonucleotides showed a weak instability of hydantoin nucleoside inserted into the oligonucleotide chain. Several enzymatic experiments aimed at determining the biochemical features of such a DNA lesion were carried out. Thus, processing of 5-OH-5-Me-dHyd by nuclease P-1, snake venom phosphodiesterase, and calf spleen phosphodiesterase was investigated. The specificity and the mechanism of excision of the lesion by several bacterial and yeast DNA N-glycosylases, namely, endonuclease III (endo III), endonuclease VIII (endo VIII), formamidopyrimidine DNA N-glycosylase (Fpg), Ntg1 protein (Ntg1), Ntg2 protein (Ntg2), and Ogg1 protein (yOgg1), were also determined. These repair studies clearly showed that all these enzymes, with the exception of the yOgg1 protein, are able to recognize and remove 5-hydroxy-5-methylhydantoin from the double-stranded DNA fragment. Finally, a 22-mer DNA oligomer bearing a 5-OH-5-Me-dHyd residue was used as a template to study the in vitro nucleotide incorporation opposite the damage by the Klenow fragment of Escherichia coli polymerase I, Taq DNA polymerase, and DNA polymerase beta. Thus, it may be concluded that the oxidized thymine residue is a strongly blocking lesion for the three studied DNA polymerases.