(S)-5?-C-Aminopropyl-2?-O-methyl nucleosides enhance antisense activity in cultured cells and binding affinity to complementary single-stranded RNA
نویسندگان
چکیده
Antisense oligonucleotides (ASOs) are a promising clinical tool that could be applied for unmet medical needs, but there several limitations their therapeutic application. Here, we designed and synthesized ( S )-5?- C -aminopropyl-2?- O -methylcytidine, containing -methyluridine -methylcytidine. We then investigated the properties of ASOs these nucleoside analogs. -Aminopropyl modifications enhanced thermal stability DNA/RNA duplexes when compared to other commercially available 2?- -methyl modifications. This suggested terminal ammonium cation on alkyl side chains neutralized negative charge phosphates in duplex. Additionally, overall conformation ASO/RNA was retained with modified ASOs. Thus, exhibited ability elicit RNase H activity. Furthermore, found -aminopropyl modification higher antisense potency than those cultured cells. Therefore, nucleosides this study candidates developing therapeutics.
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry
سال: 2021
ISSN: ['1464-3391', '0968-0896']
DOI: https://doi.org/10.1016/j.bmc.2020.115925