The Trana Staphylococcus aureus 201 High-Throughput (HTS) Assay identifies compounds that inhibit the essential use of a S. aureus unique tRNAArg that is required for protein synthesis. The assay identifies compounds that interfere with the interaction of an oligonucleotide mimic of the ASL loop of tRNAArg with a programmed ribosome.The validated assay was used to screen a 60,000 compound library from which 283 compounds were initially identified. These compounds were retested in a dose response curve and 89 compounds were confirmed as biochemically active.
Thirty-eight of these compounds were selected based on an acceptable IC50 concentration and tested in a bacterial assay where eight compounds demonstrated activity against two or more strains of S. aureus. Strains tested included MRSA strains, vancomycin resistant strains and MDR strains. The two most active hits were further characterized to establish a true antibiotic effect.
Further experiments with all eight bioactive hits demonstrated that six of the eight inhibited polypeptide synthesis directly.
The assay is now fully HTS functional and is immediately available for licensing to the pharmaceutical industry for the discovery, development, and market availability of critically needed new anti-infectives.
