Discovery of a Structurally Unique Small Molecule that Inhibits Protein Synthesis

Identifying and characterizing natural products and synthetic small molecules that inhibit biochemical processes such as ribosomal translation can lead to novel sources of molecular probes and therapeutics. The search for new antibiotics has been invigorated by the increasing burden of drug-resistant bacteria and has identified many clinically essential prokaryote-specific ribosome inhibitors. However, the current cohort of antibiotics is limited with regards to bacterial resistance mechanisms because of structural similarity within classes. From a high-throughput screen for translation inhibitors, we discovered a new compound, T6102, which inhibits bacterial protein synthesis in vitro, inhibits bacterial growth of Bacillus subtilis in vivo, and has a chemical structure that appears to be unique among known classes of translation-inhibiting antibiotics. T6102’s unique structure compared to current clinically-utilized antibiotics makes it an exciting new candidate for the development of next-generation antibiotics.