Design of Multimodal Small Molecules Targeting miRNAs Biogenesis: Synthesis and In Vitro Evaluation

Methods Mol Biol. 2017:1517:137-154. doi: 10.1007/978-1-4939-6563-2_10.

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.

Keywords: DICER cleavage; Inhibitors; Ligands; Synthetic small molecules; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / genetics*
  • Gene Expression Regulation / drug effects
  • Humans
  • Ligands
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Molecular Biology / methods*
  • RNA / genetics
  • Ribonuclease III / antagonists & inhibitors
  • Ribonuclease III / genetics*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / therapeutic use

Substances

  • Ligands
  • MicroRNAs
  • Small Molecule Libraries
  • RNA
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases