Characterization of Novel Antimicrobial Peptoids

Abstract

Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 μg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity againstStaphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. β-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 molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

In vitro antifungal activity of indirubin isolated from a South Indian ethnomedicinal plant Wrightia tinctoria R. Br.

“…Indirubin (200 mg/ml in DMSO) was added into MH broth and tested in twofold serial dilutions from 200 g/ml. The final inoculum size was approximately 5 × 10 5 cfu/ml for Candida and 1 × 10 4 spores/ml for filamentous fungi (Goodson et al, 1999). The final DMSO concentration was maintained as less than 1%.…”

Strategies employed in the design and optimization of synthetic antimicrobial peptide amphiphiles with enhanced therapeutic potentials

“…Owing to their protease stability as well as the synthetic ease and versatility of introducing a wide variety of functional groups containing a primary amine [121], amphiphilic peptoids are attractive as AMP mimics and have been demonstrated to be effective against various human pathogens [122][123][124]. In the study by Barron's group, a library of rationally designed amphiphilic helical peptoids were demonstrated to have low-micromolar antibacterial activities similar to that mediated by pexiganan and melittin and that the antimicrobial trends in relation to structure and amphipathicity follow closely to that observed with conventional AMPs [122].…”

Synthesis and biological activity of 1,3,4-oxa(thia)diazole, 1,2,4-triazole-5-(thio)one and S-substituted derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid

“…Tryptic soy agar (TSA) and tryptic soy broth (TSB) were used for bacteria cultivation and antibacterial activity tests. Antimicrobial activity of the compounds was determined by testing their different concentrations against B. cereus, S. aureus, E. coli, P. aeruginosa and C. albicans strains by the broth-dilution and spread plate methods [32,33] [34]. Minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that inhibits the visible growth of a microorganism after overnight incubation.…”