Difluoroacetic acid: an alternative acid in the detritylation reaction for the solid-phase synthesis of oligonucleotides

Nucleosides Nucleotides Nucleic Acids. 2024 Apr 11:1-9. doi: 10.1080/15257770.2024.2337145. Online ahead of print.ABSTRACTDichloroacetic acid or trichloroacetic acid are commonly used in the detritylation reaction of the automated solid-phase synthesis of oligonucleotides. Dichloroacetic acid, however, is often contaminated with trichloroacetaldehyde (chloral), leading to the formation of inseparable impurities in the final oligonucleotide product. In this work, three different sequences, namely T18, d(TAA)6, and an 18-mer mixed sequence, were used as models to compare the deprotection efficiency of three acids: trichloroacetic acid, dichloroacetic acid, and difluoroacetic acid. Comparable purities of full-length products were obtained for the synthesis of the three model sequences when dichloroacetic acid or difluoroacetic acid were used during the detritylation reaction, however, conditions need to be optimized for the synthesis of purine-rich sequences. Therefore, difluoroacetic acid is a potential alternative to dichloroacetic acid in the solid-phase synthesis of oligonucleotides to avoid the impurity formation due to presence of chloral.PMID:38602371 | DOI:10.1080/15257770.2024.2337145

Source: Nucleosides, Nucleotides and Nucleic Acids - April 11, 2024 Category: Biochemistry Authors: Quanjian Li Dhruval Joshi Yogesh S Sanghvi Hongbin Yan Source Type: research