Novel lead compounds that target the ribosomal peptidyl transferase center

The enormous complexity of the ribosome poses a barrier for drug discovery. We have overcome this in a tractable way by using an RNA segment that represents the peptidyl transferase center as a target. By using a novel combination of NMR transverse relaxation times (T2) and computational chemistry approaches, we have obtained improved inhibitors of the M. tuberculosis (Mtb) ribosomal PTC. Two phenylthiazole containing inhibtors were tested by transcription-translation biochemical assay. Their low IC50 values indicate high efficiency, which was significantly improved compared to standard antibiotic drugs. In-line probing assay confirms a specific binding of our inhibitors to the RNA-PTC.