磺酰胺类反义寡核苷酸的分子构建。

Molecular Construction of Sulfonamide Antisense Oligonucleotides.

机构信息

School of Chemistry , University of Glasgow , Joseph Black Building, University Avenue , Glasgow G12 8QQ , U.K.

Department of Pure and Applied Chemistry , University of Strathclyde , 295 Cathedral Street , Glasgow G1 1XL , U.K.

出版信息

J Org Chem. 2019 Sep 6;84(17):10635-10648. doi: 10.1021/acs.joc.9b00941. Epub 2019 Aug 19.

DOI:10.1021/acs.joc.9b00941

PMID:31379169

Abstract

An efficient and scalable synthesis of new oligonucleotide monomers was developed for replacement of the phosphodiester backbone of RNA by a sulfonamide-containing backbone to enable construction of sulfonamide antisense oligonucleotides (SaASOs). It was shown that by employing these sulfonamide RNA (SaRNA) monomers, it was possible to synthesize oligomers in solution. The properties of a sulfonamide moiety replacement were evaluated by incorporation of a SaRNA-monomer into a DNA strand and performing thermal stability tests of the resulting DNA and RNA-double-strand hybrids. Although sulfonamide modification caused a decrease in melting temperature () of both hybrids, it was lower for the sulfonamide-containing DNA-RNA hybrid than that for the sulfonamide-containing DNA-DNA hybrid.

摘要

开发了一种高效且可扩展的新寡核苷酸单体合成方法，通过含有磺酰胺的骨架替代 RNA 的磷酸二酯骨架，从而构建磺酰胺反义寡核苷酸（SaASO）。结果表明，通过使用这些磺酰胺 RNA（SaRNA）单体，可以在溶液中合成寡聚物。通过将 SaRNA 单体掺入 DNA 链中，并对所得 DNA 和 RNA 双链杂种的热稳定性测试，评估了磺酰胺部分取代的性质。尽管磺酰胺修饰导致两种杂种的熔点（T m）降低，但含磺酰胺的 DNA-RNA 杂种的 T m 降低幅度低于含磺酰胺的 DNA-DNA 杂种。