Synthesis of 3 '-S-phosphorothiolate oligonucleotides for their potential use in RNA interference
Gaynor, J. W., Brazier, J. and Cosstick, R. (2007) Synthesis of 3 '-S-phosphorothiolate oligonucleotides for their potential use in RNA interference. Nucleosides Nucleotides & Nucleic Acids, 26 (6-7). pp. 709-712. ISSN 1525-7770
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To link to this article DOI: 10.1080/15257770701490753
The potency of RNA interference (RNAi) undoubtedly can be improved through chemical modifications to the small interfering RNAs (siRNA). By incorporation of the 3′-S-phosphorothiolate modification into strands of RNA, it is hoped that specific regions of a siRNA duplex can be stabilised to enhance the target binding affinity of a selected antisense strand into the activated RNA-induced silencing complex (RISC*). Oligonucleotides composed entirely of this modification are desirable so unconventional 5′ → 3′ synthesis is investigated, with initial solution-phase testing proving successful. The phosphoroamidite monomer required for solid-phase synthesis has also been produced.