Xuan Zhou, Xianglin Shi, Yannick Fillon, Firoz Antia, Thomas Pickel, Jing Yang, William Zhang, Armin Delavari, Jiabao Zhang
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引用次数: 0
Abstract
Oligonucleotides have emerged as valuable new therapeutics. Presently, oligonucleotide manufacturing consists in a series of stepwise additions until the full-length product is obtained. Deprotection of the phosphorus backbone before cleavage and deprotection (C&D) by ammonolysis is necessary to control the 3-(2-cyanoethyl) thymidine (CNET) impurity. In this study, we demonstrate that the use of piperazine as a scavenger of acrylonitrile allows phosphorus deprotection and C&D to be combined in a single step. This reduces solvent consumption, processing time, and CNET levels. Additionally, we showed that substitution of piperazine for triethylamine in the phosphorus deprotection step of supported-synthesis leads to reduced reaction times and lower levels of CNET impurities.
期刊介绍：
Nucleic Acid Therapeutics is the leading journal in its field focusing on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. The Journal examines many new approaches for using nucleic acids as therapeutic agents or in modifying nucleic acids for therapeutic purposes including: oligonucleotides, gene modification, aptamers, RNA nanoparticles, and ribozymes.
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