C5-pyrimidine-functionalized morpholino oligonucleotides exhibit differential binding affinity, target specificity and lipophilicity. Issue 6 (12th January 2023)

• Record Type: Journal Article
• Authors: Das, Arnab; Ghosh, Atanu; Sinha, Surajit
• Is Part Of: Organic & biomolecular chemistry. Volume 21:Issue 6(2023)
• Page Start: 1242
• Page End: 1253
• Publication Date: 2023-01-12
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob01759h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : 5-Substituted cytidine and uridine greatly enhance the duplex stability of PMOs with complementary DNA and RNA for better antisense applications. Abstract : 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.