Fig. 6: Impact on covalent RNA drug design.
From: Engineering covalent small molecule–RNA complexes in living cells
Drug-like small molecules that noncovalently bind to the preQ1 riboswitch were identified by screening strategies17. For one of these compounds (DBF), covalent tethering is demonstrated here. a, Secondary structure of the preQ1-I (nucleosides in gray and blue form the binding pocket; ligand (DBF) in cyan; reactive guanosine in yellow; same color code is used in b). b, Stick representation of the preQ1 aptamer pocket in complex with a micromolar dibenzofuran binder (DBF) (PDB 6E1U). c, Chemical structure of DBF. d, Structure-guided design of a DBF derivative with the reactive handle developed in this study (Brc3DBF). e, Covalent attachment of Brc3DBF incubated with the Tt preQ1 aptamer was confirmed by FT-ICR-MS analysis, and MS sequencing identified G4 as the primary site of alkylation (Extended Data Fig. 8).
