forapin and Pseudomonas-Infections

Topics: Animals; Antimicrobial Peptides; Antitubercular Agents; Cell Survival; Chemokines; Dose-Response Relationship, Drug; Erythrocytes; Humans; Lysine; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Pseudomonas Infections; Stereoisomerism; Structure-Activity Relationship; THP-1 Cells

Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile's helical propensity and cell selectivity. The engineered amphiphiles were also found to efficiently reduce sessile P. aeruginosa biofilm biomass, neutralize endotoxins, inhibit the inflammatory response, and remain active under physiological salt concentrations. In summary, these findings are helpful for short AMP design with a highly therapeutic index to treat bacteria-induced infection.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biofilms; Circular Dichroism; Drug Design; Hemolysis; Humans; Models, Molecular; Peptides; Protein Structure, Secondary; Pseudomonas aeruginosa; Pseudomonas Infections; Surface-Active Agents