合成 N3-甲基尿苷和 2'-O 烷基/2'-氟-N3-甲基尿苷修饰的磷酰胺及其与 DNA 和 RNA 寡核苷酸的结合。

Avijit Sahoo, Kiran R. Gore
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引用次数: 0

摘要

本文介绍了 N3-甲基尿苷(m3U)和 2'-O-烷基/2'-氟-N3-甲基尿苷(2'-O-烷基/2'-F-m3U)磷酰胺的合成,以及将它们加入 14 聚体 DNA 和 RNA 寡核苷酸序列的过程。2'-O- 烷基-m3U 亚磷酰胺的合成首先使用市售的尿苷,以获得三苯甲基化的 m3U 中间体,然后进行 2'-O- 烷基化,最后进行磷酸化。2'-F-m3U 亚磷酰胺是从市售的 2'-F 尿苷核苷中合成的。这些亚磷酰胺单体与使用传统亚磷酰胺化学方法合成 DNA 和 RNA 寡核苷酸兼容。这种策略提供了在 m3U 的 2'- 位进行各种修饰的高效合成途径,可用于多种基于核酸的治疗应用,包括反义技术、小干扰 RNA、CRISPR-Cas9 和适配体。本文中的数据基于我们之前发表的报告。© 2024 Wiley Periodicals LLC.基本方案 1:2'-O-烷基-N3-甲基尿苷类似物及其相应亚磷酰胺的合成 替代方案 1:2'-O-TBDMS-N3-甲基尿苷及其亚磷酰胺的合成 替代方案 2:2'-氟-N3-甲基尿苷及其亚磷酰胺的合成 基本方案 2:N3-甲基尿苷修饰的 DNA 和 RNA 寡核苷酸的固相合成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis of N3-Methyluridine- and 2′-O-Alkyl/2′-Fluoro-N3-Methyluridine-Modified Phosphoramidites and Their Incorporation into DNA and RNA Oligonucleotides

In this article, we describe the synthesis of N3-methyluridine (m3U) and 2′-O-alkyl/2′-fluoro-N3-methyluridine (2′-O-alkyl/2′-F-m3U) phosphoramidites as well as their incorporation into a 14-mer DNA and RNA oligonucleotide sequence. Synthesis of the 2′-O-alkyl-m3U phosphoramidite starts with commercially available uridine to achieve a tritylated m3U intermediate, followed by 2′-O-alkylation and finally phosphitylation. Synthesis of the 2′-F-m3U phosphoramidite is obtained from a commercially available 2′-F-uridine nucleoside. These phosphoramidite monomers are compatible with DNA and RNA oligonucleotide synthesis using conventional phosphoramidite chemistry. This strategy offers efficient synthetic access to various modifications at the 2′-position of m3U that can be employed in numerous nucleic acid–based therapeutic applications, including antisense technologies, small interfering RNAs, CRISPR-Cas9, and aptamers. The data presented in this article are based on our previously published reports. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of 2′-O-alkyl-N3-methyluridine analogs and their corresponding phosphoramidites

Alternate Protocol 1: Synthesis of 2′-O-TBDMS-N3-methyluridine and its phosphoramidite

Alternate Protocol 2: Synthesis of 2′-fluoro-N3-methyluridine and its phosphoramidite

Basic Protocol 2: Solid-phase synthesis of N3-methyluridine-modified DNA and RNA oligonucleotides

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