title: Design of Multimodal Small Molecules Targeting miRNAs Biogenesis: Synthesis and In Vitro Evaluation.
abstract: microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported.
authors.affiliation: Institute of Chemistry of Nice, University of Nice Sophia Antipolis, UMR7272 CNRS, Parc Valrose, 06100, Nice, France.
authors.forename: Duc D
authors.initials: DD
authors.lastname: Vo
authors.affiliation: Institute of Chemistry of Nice, University of Nice Sophia Antipolis, UMR7272 CNRS, Parc Valrose, 06100, Nice, France. maria.duca@unice.fr.
authors.forename: Maria
authors.initials: M
authors.lastname: Duca
mesh_terms: D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008967:Molecular Biology / Q000379:methods*; D012313:RNA / Q000235:genetics; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D008024:Ligands; D035683:MicroRNAs; D054852:Small Molecule Libraries; D012313:RNA; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER cleavage; Inhibitors; Ligands; Synthetic small molecules; microRNAs