CHEMICAL SYNTHESIS OF A NEW MATERIAL OF ANTISENSE NUCLEIC ACID"2"PHOSTHORYLATEDRNAS" DIRETED TOWARD IIS BASIC STRUCTRAL STUDIES AND REGULATION OF EXPRESSION OF HIV VIRUS-

针对 IIS 基础结构研究和 HIV 病毒表达调控的反义核酸新材料“2”磷酸化 RNA 的化学合成-

• 批准号: 04453031
• 负责人: SEKINE Mitsuo
• 金额: $ 4.42万
• 依托单位: TOKYO INSTITUTE OF TECHNOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04453031/
• 关键词: ANTISENCE NUCLEIC ACID; 2'-PHOSPHATE; RNA; CHEMICALSYNTHESIS; HIV; SOLID PHASE SYNTHESIS; ENZYME RESISTANCE; AMIDITE; アンチセンス核酸; 酸素耐性; 2'-リン酸化RNA; アミダイト試薬; エイズ; 環状シリルエーテル; 保護基; 2'、3'-リン酸基転移; チオリン酸基

This year, we have tried to study the development of new organic reactions required for the synthesis of 2'-phosphorylated RNAs. As the result, we have achieved the following results : First, we found that bis(2-cyano-1, 1-diamethylethyl)phosphoryl can be used not only as a 2'-hydroxyl protecting groups but also as a precursor of the 2'-phosphate group. This protected phosphoryl group was found to be quite stable upon removal of a 3', 5-cyclic silyl protecting group with HF/Py in dichloromethane and not to migrate from the 3'-2' hydroxyl functions. This finding led us to realize the construction of key intermediates, 2'-phosphorylated 3'-phosphoramide units which were required throughout this study. The builiding units were utilized for the solid phase synthesis of 2'-phosohorylated yridylate derivatives. We could synthesize 2, 4, 6, and 10mers of 2'-phosphorylated uridylated uridylates in good yields. They were found to be resistant to acid and alkaline conditions as well as enzymatic digestion with spleen phosphodiesterase. In particular, the 10 mer proved to have an unique structure as evidenced by NMR.At the present time, we are studying the binding ability of these new nucleic acid derivatives for target DNA or RNA fragments.

今年，我们尝试研究合成 2'-磷酸化 RNA 所需的新有机反应的开发。结果，我们取得了以下成果：首先，我们发现双(2-氰基-1,1-二甲基乙基)磷酰基不仅可以用作2'-羟基保护基团，而且可以用作2'-羟基保护基团的前体。 '-磷酸基团。发现该受保护的磷酰基在用二氯甲烷中的HF/Py除去3'、5-环甲硅烷基保护基后非常稳定，并且不会从3'-2'羟基官能团迁移。这一发现使我们认识到了整个研究所需的关键中间体 2'-磷酸化 3'-磷酰胺单元的构建。该构建单元用于固相合成2'-磷酸化亚吡啶酯衍生物。我们可以以良好的产率合成 2'-磷酸化尿苷酸的 2、4、6 和 10 聚体。人们发现它们对酸性和碱性条件以及脾磷酸二酯酶的酶消化具有抵抗力。特别是，NMR证明了10聚体具有独特的结构。目前，我们正在研究这些新的核酸衍生物与目标DNA或RNA片段的结合能力。

项目成果

M.Sekine et al.: "Sumultaneous Removal of Two 2-Cyano-1,1-dimethylethyl Groups from Bis(2-Cyano-1,1-dimethylethyl)thymidine 3^1-Phosphate Der." Natural Products Letters. (印刷中).

M.Sekine 等人：“从双（2-氰基-1,1-二甲基乙基）胸苷 3^1-磷酸盐 Der 中同时去除两个 2-氰基-1,1-二甲基乙基”（印刷版）。 ） 期间）。

M.Sekine et al.: "Syntheses and Properties of Dansylated Deoxycytidine 3'、5'-Bisphosphate Derivatives Useful for 3'-Labeling of Oligoribonucleotides" Nucleosides & Nucleotides. 11. 1713-1730 (1992)

M.Sekine 等人：“可用于 3-标记寡核糖核苷酸的丹酰化脱氧胞苷 3, 5-二磷酸衍生物的合成和特性”核苷和核苷酸 11. 1713-1730 (1992)。

M.Sekine et al.: "Selective and Rapid O-Acylation of Hydroxyl Groups of Nucleosides by Phase Transfer Catalysis" Natural Products Letters. 1. 251-256 (1993)

M.Sekine 等人：“通过相转移催化对核苷羟基进行选择性和快速 O-酰化”天然产物快报。

M.Sekine et al.: "Synthesis and Properties of N-Tritylthio Nucleoside Dervatives" Journal Chemical Society,Perkin Trans.1. 3087-3093 (1993)

M.Sekine 等人：“N-三苯甲基硫代核苷衍生物的合成和性质”化学学会杂志，Perkin Trans.1。

M.Sekine et al.: ""Synthesis and Properties of N-Tritylthio Nucleoside Derivatives"" Joumal of Chemical Society, Perkin Trans.1. 3087-3093 (1993)

M.Sekine 等人：“N-三苯甲基硫代核苷衍生物的合成和性质”，《化学学会杂志》，Perkin Trans.1。