Optimization of automatic synthesis of benzoxazole phosphoramidate oligonucleotides

Elizaveta E. Baranoskaya ; Sofia A. Poddubnyakova ; Alexander A. Lomzov ; Svetlana V. Vasilyeva

Žurnal Sibirskogo federalʹnogo universiteta. Matematika i fizika, Tome 17 (2024) no. 6, pp. 776-782.

Résumé

Phosphoramidate benzoazole oligonucleotides (PABAO) are a newly developed oligonucleotides derivatives that carrying internucleotide N-(benzoazole)-phosphoramidate moieties. They can be obtained by the classical method of automated solid-phase phosphoramidate synthesis, in which the oxidation step is replaced by a Staudinger reaction with an azide modifier. In this work, optimization of the synthetic protocol of N-benzoxazole oligonucleotides was carried out. The optimization consisted of reducing the concentration of the azido reagent and shortening the synthesis time. With the adjustment, optimized synthesis conditions allow for a 2.5-fold decrease in benzoxazole azide consumption as well as a 20-min reduction in the time required for single modification introduction in oligonucleotide synthesis. The obtained advantages will be used for the scaled-up production of PABAOs in order to study them in biomedical applications.

Détail

Keywords: PABAO, automatic synthesis, Staudinger reaction.
Mots-clés : phosphoramidate benzoazole oligonucleotide

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