Synthesis, chirality-dependent conformational and biological properties of siRNAs containing 5'-(R)- and 5'-(S)-C-methyl-guanosine.

ABSTRACT: Various chemical modifications have been identified that enhance potency of small interfering RNAs (siRNAs) and that reduce off-target effects, immune stimulation, and toxicities of metabolites of these therapeutic agents. We previously described 5'-C-methyl pyrimidine nucleotides also modified at the 2' position of the sugar. Here, we describe the synthesis of 2'-position unmodified 5'-(R)- and 5'-(S)-C-methyl guanosine and evaluation of these nucleotides in the context of siRNA. The (R) isomer provided protection from 5' exonuclease and the (S) isomer provided protection from 3' exonuclease in the context of a terminally modified oligonucleotide. siRNA potency was maintained when these modifications were incorporated at the tested positions of sense and antisense strands. Moreover, the c

SUBMITTER: Mikami A 

PROVIDER: S-EPMC7544225 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature