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一种改进的聚(V)硫代寡核苷酸合成平台。

An Improved P(V) Thio-Oligonucleotide Synthesis Platform.

作者信息

Nassir Molhm, Gherardi Luca, Redman Richard L, Jin Yonghao, Yao Feng, Yang Yang, Raheja Nicholas, Natarajan Arjun, Butler David, Knouse Kyle W, Baran Phil S

机构信息

Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Dipartimento di Chimica e Chimica Industriale, University of Pisa, Via G. Moruzzi 13, Pisa 56124, Italy.

出版信息

Org Lett. 2025 Jan 10;27(1):97-102. doi: 10.1021/acs.orglett.4c03980. Epub 2024 Dec 19.

Abstract

Three critical advances in simplifying the adoption of P(V)-based stereopure, phosphorothioate-containing oligonucleotide synthesis are reported. A more inexpensive phosphorus-sulfur incorporation reagent () is introduced, a robust linker system was developed, and a systematic study of common nucleobase protecting groups was performed to significantly reduce the barrier to adoption of this technology.

摘要

本文报道了在简化基于磷(V)的立体纯含硫代磷酸酯寡核苷酸合成方法方面取得的三项关键进展。引入了一种更廉价的磷硫掺入试剂(),开发了一种稳健的连接系统,并对常见的核苷酸碱基保护基团进行了系统研究,以显著降低采用该技术的障碍。

相似文献

1
An Improved P(V) Thio-Oligonucleotide Synthesis Platform.一种改进的聚(V)硫代寡核苷酸合成平台。
Org Lett. 2025 Jan 10;27(1):97-102. doi: 10.1021/acs.orglett.4c03980. Epub 2024 Dec 19.
2
Unlocking P(V): Reagents for chiral phosphorothioate synthesis.解锁 P(V):手性磷硫代酸酯合成试剂。
Science. 2018 Sep 21;361(6408):1234-1238. doi: 10.1126/science.aau3369. Epub 2018 Aug 2.

本文引用的文献

1
Discovery and characterization of stereodefined PMO-gapmers targeting tau.靶向tau的立体定向PMO缺口嵌合体的发现与表征
Mol Ther Nucleic Acids. 2024 Nov 28;36(1):102404. doi: 10.1016/j.omtn.2024.102404. eCollection 2025 Mar 11.
6
Stereocontrolled Radical Thiophosphorylation.立体控制的自由基硫代磷酸化反应
J Am Chem Soc. 2023 Jul 19;145(28):15088-15093. doi: 10.1021/jacs.3c05655. Epub 2023 Jul 3.
10
A P(V) platform for oligonucleotide synthesis.一种用于寡核苷酸合成的 P(V) 平台。
Science. 2021 Sep 10;373(6560):1265-1270. doi: 10.1126/science.abi9727. Epub 2021 Sep 9.

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