Optimization of Automatic Synthesis of Benzoxazole Phosphoramidate Oligonucleotides

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