RNA-Binding Antibiotics

The past several years have seen a fundamental change in our perception of RNA. RNA was once regarded as a passive mediator of genetic information in mRNA and tRNA or as a mere scaffold for proteins in the ribosome. But the discovery of catalytic RNA, the development of SELEX, and dramatic improvements in RNA structure analysis have rather demonstrated that RNA is a highly versatile and dynamic molecule. Our increased understanding of the important role RNA plays in most, if not all, cellular processes has lead to the awareness that RNA represents a potential and prominent target for therapeutic intervention. On one hand, nature has "invented" an innumerable amount of small compounds which bind to RNA and modulate its function, on the other hand, the design and preparation of RNA molecules with defined properties is now within reach. This volume covers RNAs with known or proposed catalytic activity or functional importance whose behavior is affected by antibiotics. These include the peptidyl transferase and the decoding activities of the ribosome and the cleavage activities of several catalytic RNAs. Detailed discussion of the wide-spread effects of the tetracyclines, of the peptide antibiotic viomycin and of bleomycin on RNAs are presented. SELEX has provided a wealth of antibiotic-binding RNAs which are amenable to NMR structure determination. Detailed biophysical analyses on antibiotic-RNA interactions, and the design and synthesis of novel aminoglycosides suggest strategies for the pharmaceutical exploitation of RNA-binding drugs. On the verge of losing the battle against bacteria, which are acquiring resistance genes against all used antibiotics, it is mandatory to find new therapeutics. RNA-binding antibiotics are not only therapeutically valuable, they play a major role in the deciphering of RNA function and stimulate evolutionary thoughts about the origin of life.