C5-pyrimidine-functionalized morpholino oligonucleotides exhibit differential binding affinity, target specificity and lipophilicity.

Arnab Das, Atanu Ghosh, Surajit Sinha

Organic & biomolecular chemistry 2023 Feb 08

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C5-substituted uridine and cytidine morpholino chlorophosphoramidate monomers were synthesized and incorporated into a 12-mer Phosphorodiamidate Morpholino Oligonucleotide (PMO) using semi-automated solid phase synthesis. PMOs with most of the tested pyrimidine C5-substitutions have significantly increased thermal stability when bound to the complementary RNA strand relative to the PMO. They exhibit higher binding with RNA than DNA. CD-spectra show B-type helical conformation of duplexes. HPLC analysis indicates their greater lipophilicity compared to regular PMOs. These chemical modifications have significant potential towards the development of better antisense technologies.

Citation

Arnab Das, Atanu Ghosh, Surajit Sinha. C5-pyrimidine-functionalized morpholino oligonucleotides exhibit differential binding affinity, target specificity and lipophilicity. Organic & biomolecular chemistry. 2023 Feb 08;21(6):1242-1253