Abstract
To develop new antimicrobial synthetic lipopeptides with optimizing peptide length, cationic tripeptides RWR/WRR were N-terminal fatty acylated, and self-assembled with 1-dodecanethiol-anchored gold nanoparticles (Au-DT NPs) via hydrophobic interaction. The ultrashort lipopeptides and their nano-assemblies were effective against a variety of microorganisms, with minimal inhibitory concentrations ranging from 0.5 to 8 μg/mL. Hemolysis analysis and in vitro cytotoxicity assay revealed that self-assembling with Au-DT NPs would improve biological toxicity of lipopeptides, especially for the most active lipopeptides (Palmitoyl-RWR, Palmitoyl-WRR) with long lipid tails. As lipopeptides/ Au-DT NPs displayed slower bactericidal kinetics compared with free lipopeptides, the mode of action was further investigated. Difference in membrane targeting mechanism between lipopeptides and their nano-assemblies may be attributed to the structural architecture. The simple composition and diverse specificities of lipopeptides/Au-DT NPs, as well as their biocompatibility could make them as economically available potent antimicrobial agents for various applications.
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