Peptide-oligonucleotide conjugates exhibiting pyrimidine-X cleavage specificity efficiently silence miRNA target acting synergistically with RNase H.

ABSTRACT: Taking into account the important role of miRNA in carcinogenesis, oncogenic miRNAs are attractive molecules for gene-targeted therapy. Here, we developed a novel series of peptide-oligonucleotide conjugates exhibiting ribonuclease activity targeted to highly oncogenic miRNAs miR-21 and miR-17. When designing the conjugates, we enhanced both nuclease resistance of the targeted oligodeoxyribonucleotide by introducing at its 3'-end mini-hairpin structure displaying high thermostability and robustness against nuclease digestion and the efficiency of its functioning by attachment of the catalytic construction (amide)NH₂-Gly(ArgLeu)₄-TCAA displaying ribonuclease activity to its 5'-end. Designed miRNases efficiently cleaved miRNA targets, exhibiting Pyr-X specificity, and c

SUBMITTER: Patutina OA 

PROVIDER: S-EPMC6177439 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature