An Improved P(V) Thio-Oligonucleotide Synthesis Platform

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

doi:10.1021/acs.orglett.4c03980

An Improved P(V) Thio-Oligonucleotide Synthesis Platform

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

Scripps Research
University of Pisa
Elsie Biotechnologies
Shanghai Hongene Biotech Corporation
Socrates Biosciences Inc
Hongene Biotech Corporation

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 (Ψ^Br) 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.

Original language	English
Pages (from-to)	97-102
Number of pages	6
Journal	Organic Letters
Volume	27
Issue number	1
Early online date	19 Dec 2024
DOIs	https://doi.org/10.1021/acs.orglett.4c03980
State	Published - 10 Jan 2025
Externally published	Yes

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© 2024 American Chemical Society.

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10.1021/acs.orglett.4c03980

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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 (ΨBr) 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.",

author = "Molhm Nassir and Luca Gherardi and Redman, \{Richard L.\} and Yonghao Jin and Feng Yao and Yang Yang and Nicholas Raheja and Arjun Natarajan and David Butler and Knouse, \{Kyle W.\} and Baran, \{Phil S.\}",

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AU - Nassir, Molhm

AU - Gherardi, Luca

AU - Redman, Richard L.

AU - Jin, Yonghao

AU - Yao, Feng

AU - Yang, Yang

AU - Raheja, Nicholas

AU - Natarajan, Arjun

AU - Butler, David

AU - Knouse, Kyle W.

AU - Baran, Phil S.

PY - 2025/1/10

Y1 - 2025/1/10

N2 - 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 (ΨBr) 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.

AB - 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 (ΨBr) 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.

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An Improved P(V) Thio-Oligonucleotide Synthesis Platform

Abstract

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