ArticleAnalytical chemistry2024
Unravelling the Link between Oligonucleotide Structure and Diastereomer Separation in Hydrophilic Interaction Chromatography.
Article in Analytical chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Advances in Analysis of Therapeutic Oligonucleotides with Chromatography Coupled to Mass Spectrometry.Analytical chemistry · 2026Review
- Current CMC challenges in oligonucleotide API development: from IND to NDA.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.Non-coding RNA research · 2026Review
- The use of multiple liquid chromatography methods augmented by phosphorus-31 nuclear magnetic resonance to characterize the diastereomer composition in synthetic oligonucleotides.Journal of chromatography. A · 2026Article
- Separation of PS diastereomers in GalNAc-conjugated siRNA-a comparative study of chromatographic and ion mobility mass spectrometry approaches.Analytical and bioanalytical chemistry · 2025Article
- Recent advances in analytical separation techniques for therapeutic oligonucleotides.Bioanalysis · 2025Review
- Ion-Pairing Hydrophilic Interaction Chromatography for Impurity Profiling of Therapeutic Phosphorothioated Oligonucleotides.Analytical chemistry · 2025Article
- Quantitative Analysis of Phosphorothioate Isomers in CRISPR sgRNA at Single-Residue Resolution Using Endonuclease Digestion Coupled with Liquid Chromatography Cyclic Ion Mobility Mass Spectrometry (LC/cIMS).Analytical chemistry · 2025Article
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
- Keeping up with a Quickly Diversifying Pharmaceutical Landscape.ACS measurement science au · 2024Review
- Stationary phase effects in hydrophilic interaction liquid chromatographic separation of oligonucleotides.The Analyst · 2024Article
- Expanding the Analytical Toolbox for the Nondenaturing Analysis of siRNAs with Salt-Mediated Ion-Pair Reversed-Phase Liquid Chromatography.Analytical chemistry · 2024Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic oligonucleotides (ONs) commonly incorporate phosphorothioate (PS) modifications. These introduce chiral centers and generate ON diastereomers. The increasing number of ONs undergoing clinical trials and reaching the market has led to a growing interest to better characterize the ON diastereomer composition, especially for small interfering ribonucleic acids (siRNAs). In this study, and for the first time, we identify higher-order structures as the major cause of ON diastereomer separation in hydrophilic interaction chromatography (HILIC). We have used conformational predictions and melting profiles of several representative full-length ONs to first analyze ON folding and then run mass spectrometry and HILIC to underpin the link between their folding and diastereomer separation. On top, we show how one can either enhance or suppress diastereomer separation depending on chromatographic settings, such as column temperature, pore size, stationary phase, mobile-phase ionic strength, and organic modifier. This work will significantly facilitate future HILIC-based characterization of PS-containing ONs; e.g., enabling monitoring of batch-to-batch diastereomer distributions in full-length siRNAs, a complex task that is now for the first time shown as possible on this delicate class of therapeutic double-stranded ONs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.