ArticleACS omega2024
Detecting the Major Degradation Products of Phosphorothioate Oligonucleotides by Chemical Derivatization and Weak Anion Exchange Chromatography.
Article in ACS omega, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Novel polar cysteine analogues have been synthesized for the derivatization of oligonucleotide depurination impurities that may be formed under acidic conditions. Depurination impurities belong to a group that includes deamination and phosphate diester impurities, which are similar in chemical structure to each other and the parent oligonucleotide, and thus coelute by most chromatographic separation methods. The polar cysteine analogues react with depurination impurities and enable their complete separation from the parent oligonucleotide by weak anion exchange (WAX) chromatography. Optimized conditions for the derivatization reaction and the WAX analysis are presented. The ability of the WAX method to chromatographically separate deamination and phosphate diester impurities is also demonstrated, and therefore, the combination of chemical derivatization and WAX chromatography permits detection and quantification of the three major degradation products of phosphorothioate (PS) oligonucleotides.
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