Peptide quinoline conjugates: a new class of RNA-binding molecules

[reaction: see text] A synthesis of 4,8-disubstituted 2-phenylquinoline amino acids is reported with the incorporation of one example into a peptide by solid-phase synthesis. The phenylquinoline-containing peptide binds an RNA target with nanomolar affinity (K(D) = 208 nM). The strategy can be used to prepare a variety of 2-substituted quinoline amino acids for alteration of affinity in intercalator peptides. Since quinolones represent an important class of antibacterials, these compounds may be useful in the discovery of new antibacterial agents.