RNA as a drug target: The case of aminoglycosides

Abstract

How to prevent antibiotic therapies from hitting a snag: Most antibiotics target molecular switches on the ribosome. The binding sites are discrete and made of conserved RNA residues rather than ribosomal proteins (see representation of paromycin binding to the ribosome). However, bacteria have evolved and mutated so that the antibiotics cannot bind. At least two types of new molecules could be designed to keep up in this race against evolution: 1) drugs that would bind to the mutated bacterial sites but not (to avoid toxicity) with human cytoplasmic and mitochondrial ribosomes, and 2) drugs that would interfere with other molecular switches involved in translation or regulation pathways.