Spin Labeled Nucleoside Analogues: 4′-Hydroxymorpholin-2′-Ylpurines and Pyrimidines

Tronchet, J. M. J.; Zsely, M.; Cabrini, Daniel; Jorand, Chantal; Barbalat-Rey, Françoise; Komáromi, István; Ricca, Alessandra; Geoffroy, Michel

doi:10.1080/07328319308019016

Cited by 8 publications

(1 citation statement)

References 19 publications

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“…For this purpose, we synthesised morpholino-urdine (MNA-U) phosphoramidite, which is compatible with other nucleotide chemistries, to synthesise mixmer AOs using an oligonucleotide synthesiser. Towards the synthesis, the DMTr-protected uridine 1 [18] was first converted to dialdehyde 2 using classical sodium periodate-mediated oxidation in a quantitative yield, and the crude aldehyde 2 was further treated with hydroxyl amine hydrochloride to yield corresponding dioxime 3 in good yield (71%), which was purified by silica gel chromatography [19,20]. The treatment of dioxime 3 with pyridine-borane complex at room temperature gave DMTr-protected morpholino-uridine nucleoside 4 in 46% yields (slightly DMTr-group deprotection was observed under these conditions) [19].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a Morpholino Nucleic Acid (MNA)-Uridine Phosphoramidite, and Exon Skipping Using MNA/2′-O-Methyl Mixmer Antisense Oligonucleotide

Chen

Rahimizadeh

et al. 2016

Molecules

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Abstract:In this study, we synthesised a morpholino nucleoside-uridine (MNA-U) phosphoramidite and evaluated the potential of a MNA-modified antisense oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes in vitro towards extending the applicability of morpholino chemistry with other nucleotide monomers. We designed, synthesised, and compared exon skipping efficiencies of 20 mer MNA-modified 2 -O-methyl RNA mixmer AO on a phosphorothioate backbone (MNA/2 -OMePS) to the corresponding fully modified 2 -O-methyl RNA AO (2 -OMePS) as a control. Our results showed that the MNA/2 -OMePS efficiently induced exon 23 skipping. As expected, the 2 -OMePS AO control yielded efficient exon 23 skipping. Under the applied conditions, both the AOs showed minor products corresponding to exon 22/23 dual exon skipping in low yield. As these are very preliminary data, more detailed studies are necessary; however, based on the preliminary results, MNA nucleotides might be useful in constructing antisense oligonucleotides.

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