DEVELOPMENT OF NOVEL SPIN-LABELED NUCLEOSIDES

新型自旋标记核苷的开发

• 批准号: 13672220
• 负责人: ASO Mariko
• 金额: $ 2.62万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672220/
• 关键词: Spin-labeled nucleoside; N-tert-butylaminoxyl; radical; N-tert-butylaminoxyl

We designed a new type of spin-labeled nucleosides with an N-tert-butyl aminoxyl raical which is introduced to nucleobase directly. Purine and pyrimidine nucleosides with aminoxyl radical were synthesized to investigate stability and behavior of N-tert-butyl aminoxyl radical on nucleobase.1) EPR spectra of 6-N-tert-butyl aminoxyl uridine (1a) and 6-N-tert-butyl aminoxyl cytidine (2a) were measured. The aN value of 2a decreased in the presence of 10 equiv. of guanosine derivatives (12.7 gauss) compared to that of 2a itself (13 gauss).2) In order to study EPR spectra of oligonucleotide containing 2'-deoxy 6-N-tert-butyl aminoxyl uridine (4), 3, the precursor of radical, was incorporated into 15-mer. Unfortunately, the Tm value of 15-mer containing 3 decreased considerably compared to natural type 15-mer and EPR studies of 4 containing oligonucleotide were not done.3) We planned to synthesis of 2'-deoxy 5-N-tert-hydroxylamino uridine (5) and 2-N-tert-hydroxylamino inosine (6), which might have anti conformation and their incorporation into oligonucleotide might not disturb stable duplex formation. We successfully synthesized 5 via metal halogen exchange reaction of 2'-deoxy 5-iodouridine sodium salts. We also synthesized 6.

我们设计了一种新型自旋标记核苷，其带有直接引入核碱基的 N-叔丁基氨氧基基团。合成了带有氨氧基的嘌呤和嘧啶核苷，以研究 N-叔丁基氨氧基自由基在核碱基上的稳定性和行为。1) 6-N-叔丁基氨氧基尿苷 (1a) 和 6-N-叔丁基的 EPR 谱测量氨氧基胞苷(2a)。 2a 的 aN 值在 10 当量存在下下降。鸟苷衍生物 (12.7 高斯) 与 2a 本身 (13 高斯) 的比较。2) 为了研究含有 2'-脱氧 6-N-叔丁基氨氧基尿苷 (4)、3、前体的寡核苷酸的 EPR 光谱自由基，被并入15聚体。不幸的是，与天然型15聚体相比，含有3的15聚体的Tm值显着降低，并且没有对含有4的寡核苷酸进行EPR研究。3)我们计划合成2'-脱氧5-N-叔羟氨基尿苷(5) 和 2-N-叔羟氨基肌苷 (6)，它们可能具有反构象，并且它们并入寡核苷酸中可能不会干扰稳定的双链体形成。我们通过2'-脱氧5-碘尿苷钠盐的金属卤素交换反应成功合成了5。我们还合成了6。

项目成果

M.Aso et al.: "A simple and efficient method for synthesis of 5-substituted 2'-deoxy-uridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt"Chem.Commun.. 1094-1095 (2003)

M.Aso 等人：“利用 5-碘-2-脱氧尿苷钠盐的金属-卤素交换反应合成 5-取代 2-脱氧尿苷核苷的简单有效方法”Chem.Commun. 1094

M.Aso et al.: "Synthesis and properties of a new class of nucleosides with spin source"Nucleic Acids Research Supplement. 1. 115-116 (2001)

M.Aso 等人：“具有自旋源的新型核苷的合成和特性”核酸研究增刊。

M. Aso et al.: "A simple and efficient method for synthesis of 5-substituted 2'-deoxy-uridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt"Chem. Commun. 1094-1095 (2003)

M. Aso 等人：“利用 5-碘-2-脱氧尿苷钠盐的金属-卤素交换反应合成 5-取代 2-脱氧-尿苷核苷的简单有效的方法”Chem.

M.Aso et al.: "Synthesis and Properties of N-t-butylaminoxyl Nucleosides"Nucleic Acids Research Supplement. 139-140 (2002)

M.Aso 等人：“N-叔丁基氨氧基核苷的合成和性质”核酸研究增刊。

M.Aso et al.: "Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butyl arminoxyl radicals"J.Org.Chem.. 66. 3513-3520 (2001)

M.Aso 等人：“带有 N-叔丁基氨氧基自由基的新型自旋标记核糖核苷的分子设计”J.Org.Chem.. 66. 3513-3520 (2001)