2'-O-(N-甲基氨基羰基乙基) 5-甲基-2-硫代尿苷的合成及其在剪接转换寡核苷酸中的应用。

Synthesis of 2'-O-(N-methylcarbamoylethyl) 5-methyl-2-thiouridine and its application to splice-switching oligonucleotides.

机构信息

Department of Life Science and Technology, Tokyo Institute of Technology, 4259 J2-16, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.

Department of Neurology and Neurological Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

出版信息

Bioorg Med Chem Lett. 2019 Jan 15;29(2):160-163. doi: 10.1016/j.bmcl.2018.12.005. Epub 2018 Dec 4.

DOI:10.1016/j.bmcl.2018.12.005

PMID:30551900

Abstract

The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5-methyl-2-thiouridine (sT), a duplex-stabilizing nucleotide with an MCE modification, into SSOs further improved splice switching. These SSOs may be useful for the treatment of genetic diseases associated with splicing errors.

摘要

系统评估了 2'-O-(N-甲基氨基甲酰基)乙基（MCE）修饰对剪接转换寡核苷酸（SSO）的影响。在 SSO 的 5'-末端掺入五个 MCE 核苷酸可有效提高剪接转换效果。此外，将 2'-O-(N-甲基氨基甲酰乙基）-5-甲基-2-硫代尿苷（sT）掺入 SSO 中，一种具有 MCE 修饰的双链稳定核苷酸，进一步提高了剪接转换。这些 SSO 可能对治疗与剪接错误相关的遗传疾病有用。