New approaches to target RNA binding proteins

Curr Opin Chem Biol. 2021 Jun:62:13-23. doi: 10.1016/j.cbpa.2020.12.006. Epub 2021 Jan 31.

Abstract

RNA binding proteins (RBPs) are a large and diverse class of proteins that regulate all aspects of RNA biology. As RBP dysregulation has been implicated in a number of human disorders, including cancers and neurodegenerative disease, small molecule chemical probes that target individual RBPs represent useful tools for deciphering RBP function and guiding the production of new therapeutics. While RBPs are often thought of as tough-to-drug, the discovery of a number of small molecules that target RBPs has spurred considerable recent interest in new strategies for RBP chemical probe discovery. Here we review current and emerging technologies for high throughput RBP-small molecule screening that we expect will help unlock the full therapeutic potential of this exciting protein class.

Keywords: Chemical probes; Chemoproteomics; High throughput screening (HTS); RNA binding proteins (RBPs).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Binding Sites
  • Fluorescence Resonance Energy Transfer
  • High-Throughput Screening Assays / methods*
  • Humans
  • Models, Molecular
  • Molecular Probes / chemistry
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / metabolism
  • Protein Binding
  • Protein Conformation
  • RNA-Binding Proteins / chemistry*
  • Small Molecule Libraries / chemistry*

Substances

  • Molecular Probes
  • RNA-Binding Proteins
  • Small Molecule Libraries