2-Deoxystreptamine as a platform to design original inhibitors of oncogenic miRNA biogenesis

MicroRNAs are small non-coding RNAs playing a key role in the regulation of gene expression. The overexpression of microRNAs in cancer has been recognized not only as a specific biomarker but also as a potential target to inhibit cancer cell proliferation or increase their sensitivity to chemotherapy. In this work, we present 2-deoxystreptamine as an ideal platform for the design and synthesis of selective RNA binders directed against the biogenesis of an oncogenic microRNA: miR-372. The developed compounds have been designed to bind to the structured precursor of this microRNA and block its processing toward the mature miRNA (miR-372). The performed affinity and selectivity studies revealed that one of the prepared binders is particularly selective for the targeted miRNAs and shows a very promising activity in inhibiting the production of the mature miRNAs.