The mechanism of action of DuP 721, a new antibacterial agent: Effects on macromolecular synthesis

Abstract Pulse labeling studies with Bacillus subtilis showed that DuP 721 inhibited protein synthesis. The IC 50 of DuP 721 for protein synthesis was 0.25 μg/ml but it was > 32 μg/ml for RNA and DNA synthesis. In cell-free systems, DuP 721 concentrations up to 100 μM did not inhibit peptide chain elongation reactions under conditions where chloramphenicol, tetracycline and hygromycin B inhibited these reactions. Furthermore, DuP 721 did not cause phenotypic suppression of nonsense mutations suggesting that DuP 721 did not inhibit peptide chain termination. Thus, the mechanism of action of DuP 721 is at a target preceeding chain elongation.