Inhibitors Targeting Riboswitches and Ribozymes

Evidence accumulated over the past few decades has overshadowed the central role traditionally attributed to proteins in biological function and placed instead the RNA at the core of all fundamental biological processes. For instance, small RNA domains, such as riboswitches and ribozymes, have been shown to play important, if not essential, roles in a variety of cell functions, including regulation of gene expression. Currently, a large number of clinically relevant antibiotics target the ribosome, in particular its functional RNA component [1–4]; this indicates that, owing to its structural characteristics and complexity, the RNA is a suitable and efficient target for functional inhibition by small molecules. Similar to the interaction of proteins with small molecular ligands, the complex 3D structure of the RNA offers binding pockets and surfaces that provide hydrogen bonding, base stacking, ion pairing, and hydrophobic interactions for the specific binding of diverse compounds. In light of these premises, it is tempting to venture into novel paths in antibiotic research by exploiting small, functional RNA elements such as riboswitches and ribozymes as alternative targets for the design of novel antimicrobial compounds.