Synthesis and antibacterial properties of carbohydrate-templated lysine surfactants

The synthesis of four dicationic glucose-templated d-lysine-derived surfactants and their two unmodified d-lysine-analogs is described. Replacement of d-lysine by d-glucose-templated-d-lysine provides a general tool to introduce chemical diversity into the side chain of lysine. The presence of the polyfunctional d-gluco-configured polyol scaffold provides rich opportunities to study structure–activity relationships in lysine–lipid conjugates. All cationic lipids were tested for inhibition of bacterial growth using a panel of clinically relevant Gram-positive and Gram-negative strains. Our results show that substitution of d-lysine by d-glucose-templated d-lysine surfactants retains, but does not improve, the antibacterial activity. Similarly, conversion of the d-gluco-based polyol scaffold into a hydrophobically enhanced tri-O-phenylcarbamate scaffold does not further enhance the antibacterial activity of the cationic lipid. However, improvements in the antibacterial activity were observed by guanidinylation of the two lysine-based amino groups.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide