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Simplified Oligonucleotide Phosphorus Deprotection Process with Reduced 3-(2-Cyanoethyl) Thymidine Impurities.

Xuan ZhouXianglin ShiYannick FillonFiroz AntiaThomas PickelJing YangWilliam ZhangArmin DelavariJiabao Zhang
Published in: Nucleic acid therapeutics (2024)
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.
Keyphrases
  • sewage sludge
  • ionic liquid
  • risk assessment
  • transcription factor
  • anaerobic digestion
  • dna binding