Detecting the Major Degradation Products of Phosphorothioate Oligonucleotides by Chemical Derivatization and Weak Anion Exchange Chromatography.

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 demons

SUBMITTER: Roussis SG 

PROVIDER: S-EPMC11618427 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature