5-甲基-2'-脱氧胞苷-3'-磷酸 | 100563-09-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核糖核苷3'-磷酸盐
• 中文名称: 5-甲基-2'-脱氧胞苷-3'-磷酸
• 英文名称: 5-methyl-2'-deoxycytidine-3'-phosphate
• 英文别名: 5-Methyl-deoxycytidine 3'-monophosphate；[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate
• CAS: 100563-09-5
• 化学式: C₁₀H₁₆N₃O₇P
• 分子量: 321.227
• InChiKey: BUOKTROKRYJETC-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  氯乙醛 、 5-甲基-2'-脱氧胞苷-3'-磷酸 在 T₄ polynucleotide kinase 、 腺苷 5'-三磷酸酯-gamma-32P 作用下， 生成 ((2R,3S,5R)-3-hydroxy-5-(8-methyl-5-oxoimidazo[1,2-c]pyrimidin-6(5H)-yl)tetrahydrofuran-2-yl)methyl dihydrogen phosphate-32P
  参考文献：
  名称：

  Identification of 3,N⁴-Etheno-5-methyl-2′-deoxycytidine in Human DNA: A New Modified Nucleoside Which May Perturb Genome Methylation

  摘要：

  Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N-4-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon 5mdC) lesion in DNA in vitro. Our newly developed P-32-postlabeling method was subsequently used to detect epsilon 5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.

  DOI：

  10.1021/tx200392a
• 作为产物：
  描述：

  5’-(4,4’-二甲氧基三苯基)-3’-脱氧胸苷 2’-(2-氰乙基-N,N-二异丙基)亚磷酰胺 在 重氮乙烷 、 四氮唑 、 过氧化氢异丙苯 、 氨 作用下， 以 硝基甲烷 、 水 为溶剂， 反应 16.0h， 生成 5-甲基-2'-脱氧胞苷-3'-磷酸
  参考文献：
  名称：

  Identification of 3,N⁴-Etheno-5-methyl-2′-deoxycytidine in Human DNA: A New Modified Nucleoside Which May Perturb Genome Methylation

  摘要：

  Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N-4-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon 5mdC) lesion in DNA in vitro. Our newly developed P-32-postlabeling method was subsequently used to detect epsilon 5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.

  DOI：

  10.1021/tx200392a

文献信息

• Multi-targeted single entity conjugates
  申请人：ALNYLAM PHARMACEUTICALS, INC.

  公开号：US11053495B2

  公开（公告）日：2021-07-06

  The present invention relates, in general to, compounds, compositions and methods useful for modulating gene expression of multiple target nucleic acids by a single chemical entity.

  本发明总体上涉及通过单一化学实体调节多种靶核酸基因表达的化合物、组合物和方法。
• Inhibitor of demethylase, antitumorigenic agent, and an in vitro assay for demethylase inhibitors
  申请人：Szyf Moshe

  公开号：US20050003378A1

  公开（公告）日：2005-01-06

  The present invention relates to a DNA demethylase (dMTase) inhibitor which comprises s-adenosylmethionine, a metabolite of s-adenosylmethionine or a pharmaceutically acceptable salt thereof.

  本发明涉及一种 DNA 去甲基化酶（dMTase）抑制剂，它包括 s-腺苷蛋氨酸、s-腺苷蛋氨酸的代谢物或其药学上可接受的盐。
• MULTI-TARGETED SINGLE ENTITY CONJUGATES
  申请人：Alnylam Pharmaceuticals, Inc.

  公开号：EP3324980B1

  公开（公告）日：2021-11-10
• Identification of 3,<i>N</i>⁴-Etheno-5-methyl-2′-deoxycytidine in Human DNA: A New Modified Nucleoside Which May Perturb Genome Methylation
  作者：Jagadeesan Nair、Roger W. Godschalk、Urmila Nair、Robert W. Owen、William E. Hull、Helmut Bartsch

  DOI：10.1021/tx200392a

  日期：2012.1.13

  Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N-4-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon 5mdC) lesion in DNA in vitro. Our newly developed P-32-postlabeling method was subsequently used to detect epsilon 5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.