Synthesis of sensitive oligodeoxynucleotides containing acylated cytosine, adenine, and guanine nucleobases.

DNA Pub Date : 2025-06-01 Epub Date: 2025-05-09 DOI:10.3390/dna5020025

Komal Chillar, Rohith Awasthy, Marina Tanasova, Shiyue Fang

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Abstract

The synthesis of oligodeoxynucleotides (ODNs) containing the base-labile N ⁶-acetyladenosine (6acA), N ²-acetylguanosine (2acG), and N4-methyoxycarbonyldeoxycytidine (4mcC), as well as up to four N ⁴-acetyldeoxycytidine (4acC) modifications is described. The 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) group was used as the linker for solid phase synthesis, and the methyl Dmoc (meDmoc) group was used for the protection of the exo-amino groups of nucleobases. Deprotection and cleavage were achieved under non-nucleophilic conditions, under which the highly sensitive 4acC, 6acA, 2acG, and 4mcC were found completely stable. Among the modified nucleotides, 4acC has been found in nature, and proven beneficial to DNA duplex stability. Although 6acA, 2acG and 4mcC have not been found in nature, a synthetic route to ODNs containing them is expected to facilitate projects aimed at studying their biophysical properties as well as potential for antisense, RNAi, CRISPR, and mRNA therapeutic applications.

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含有酰化胞嘧啶、腺嘌呤和鸟嘌呤核碱基的敏感寡脱氧核苷酸的合成。

本文描述了含有碱基不稳定的n6 -乙酰腺苷（6acA）、n2 -乙酰鸟苷（2acG）和n4 -甲基羰基脱氧胞苷（4mcC）以及多达四种n4 -乙酰脱氧胞苷（4acC）修饰的寡脱氧核苷酸（ODNs）的合成。采用1,3-二硫代-2-酰基甲氧羰基（Dmoc）基团作为固相合成的连接体，采用甲基Dmoc （meDmoc）基团保护核碱基的外显氨基。在非亲核条件下实现了脱保护和裂解，在此条件下发现高度敏感的4acC， 6acA， 2acG和4mcC完全稳定。在被修饰的核苷酸中，4acC已在自然界中被发现，并被证明有利于DNA的双工稳定性。虽然6acA、2acG和4mcC尚未在自然界中被发现，但含有它们的odn的合成途径有望促进旨在研究它们的生物物理性质以及反义、RNAi、CRISPR和mRNA治疗应用潜力的项目。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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DNA

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