RNA-Binding Peptides Inspired by the RNA Recognition Motif

β-Hairpin peptides with RNA-binding sequences mimicking the central two β-strands of the RNA recognition motif (RRM) protein domain have been observed to bind in a 2:1 fashion to a series of RNA homooligonucleotides in aqueous solution (PBS buffer, pH 7.40) with binding energies (-27 to -35 kJ mol^-1) similar to those of full-size protein RRMs. The peptides display mild selectivities with respect to the binding of the different homooligomers. Binding studies in 500 mM magnesium chloride suggest that the complex formation is not predominantly driven by Coulombic attraction. These peptides represent a starting point for further studies of non-Coulombic binding of RNA by peptides and proteins, which is important in the context of contemporary biology, potential therapeutic applications, and prebiotic peptide-RNA interactions.