Improvement of chemo- and stereoselectivity for phosphorothioate oligonucleotides in capillary electrophoresis by addition of cyclodextrins.

Ghassemi K, Maryam; Demelenne, Alice; Crommen, Jacques; Servais, Anne-Catherine; Fillet, Marianne

doi:10.1016/j.chroma.2022.463270

Article (Scientific journals)

Improvement of chemo- and stereoselectivity for phosphorothioate oligonucleotides in capillary electrophoresis by addition of cyclodextrins.

Ghassemi K, Maryam; Demelenne, Alice; Crommen, Jacques et al.

2022 • In Journal of Chromatography. A, 1676, p. 463270

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/311672

DOI
10.1016/j.chroma.2022.463270

PubMed
35763948

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Keywords :

Capillary electrophoresis; Cyclodextrin; Diastereomeric separation; Short phosphorothioate oligonucleotide; Cyclodextrins; Phosphorothioate Oligonucleotides; Electrophoresis, Capillary/methods; Stereoisomerism; Cyclodextrins/chemistry; Background electrolytes; Chemical alteration; Chemo-selectivity; Optimisations; Phosphorothioate modifications; Phosphorothioate oligonucleotide; Physicochemical property; Electrophoresis, Capillary; Analytical Chemistry

Abstract :

[en] Phosphorothioate (PS) modification is one of the most widely used oligonucleotide chemical alterations in the oligonucleotide backbone. It has proven to be crucial in the field of therapeutic oligonucleotides regarding the optimization of their physicochemical and biological properties. In this study, a capillary electrophoresis (CE) method with an acidic background electrolyte (BGE) containing a combination of β- and γ-cyclodextrins derivatives as chiral selectors is proposed for the diastereomeric separation of 5-mer oligonucleotides containing 0, 1, 2, or 3 phosphorothioate linkages (5´-TCGTG-3´). The effects of the BGE pH, organic modifier addition, and type of cyclodextrin (CD) on chemo- and stereoselectivity and resolution were studied. A mixture of 25 mM (2-hydroxy-3-N,N,N-trimethylamino)propyl-γ-CD and 10 mM carboxymethyl-β-cyclodextrin in a pH 3 buffer was found to be the most appropriate system for the qualitative evaluation of the short oligonucleotides investigated. These phosphorothioate oligonucleotides were separated with high efficiency in less than 11 min with no capillary treatment. The suggested approach can be the basis for purity testing of this new generation of therapeutics.

Research Center/Unit :

CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Ghassemi K, Maryam; Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Quartier hopital, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: marianne.fillet@uliege.be

Demelenne, Alice ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Crommen, Jacques ; Université de Liège - ULiège > Département de pharmacie

Servais, Anne-Catherine ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Language :

English

Title :

Improvement of chemo- and stereoselectivity for phosphorothioate oligonucleotides in capillary electrophoresis by addition of cyclodextrins.

Publication date :

02 August 2022

Journal title :

Journal of Chromatography. A

ISSN :

0021-9673

eISSN :

1873-3778

Publisher :

Elsevier B.V., Netherlands

Volume :

1676

Pages :

463270

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0021967322004630?httpAccept=text/xml

Funders :

Fonds Léon Fredericq
ULiège - Université de Liège

Funding text :

Authors thank the University of Liege, and the Fondation Léon Frédéricq for the financial support.

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since 22 January 2024

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