Characterization of novel antimicrobial peptoids

Peptoids differ from peptides in that peptoids are composed of N-substitute d rather than alpha-carbon-substituted glycine units. In this paper,re repo rt the in vitro and in vivo antibacterial activities of several antibacteri al peptoids discovered by screening combinatorial chemistry libraries for b acterial growth inhibition, In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 mu g/ml against a panel of g ram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Stap hylococcus aureus was rapid, bactericidal, and independent of protein synth esis. beta-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the mo lecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.