Mechanistic Insights Into the Retention and Separation Mechanism of Poly(Ethylene Glycol)-Modified Short Oligonucleotides in Anion-Exchange Chromatography.

ABSTRACT: Purification is a critical step in the development of synthetic short DNA for pharmaceutical applications. PEGylation enhances stability and pharmacokinetics but introduces steric and hydration effects that affect chromatographic behavior without altering the nominal DNA charge. This study investigated the retention and mass-transfer behavior of thymine-based poly(dT) oligomers (9-95 bases) modified with poly(ethylene glycol) (PEG) using anion-exchange chromatography with a mechanistic ion-exchange framework. By systematically varying PEG molecular weight and modification site, we examined how PEG-induced changes in molecular size and local interaction environment are reflected in mechanistic retention parameters. PEGylation shifted elution to lower salt concentrations, with more pronounce

SUBMITTER: Yoshimoto N 

PROVIDER: S-EPMC12835577 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature