title: Synthesis and antibacterial properties of carbohydrate-templated lysine surfactants.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Manitoba, R3T 2N2 Winnipeg, Manitoba, Canada.
authors.forename: Dhananjoy
authors.initials: D
authors.lastname: Mondal
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Frank
authors.initials: F
authors.lastname: Schweizer
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005601:Framycetin / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D013501:Surface-Active Agents; D005601:Framycetin; D008239:Lysine