title: Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.
abstract: RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.
authors.affiliation: The Department of Chemistry, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Tuan
authors.initials: T
authors.lastname: Tran
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Disney
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D009579:Nitrobenzoates / Q000737:chemistry; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D011726:Pyridinium Compounds / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D054852:Small Molecule Libraries
chemical_list: D001562:Benzimidazoles; D007211:Indoles; D009579:Nitrobenzoates; D011726:Pyridinium Compounds; D054852:Small Molecule Libraries; C533175:pyridinium 2,4-dinitrobenzoate; D012313:RNA; C030374:indole