Novel Design of Heptad Amphiphiles To Enhance Cell Selectivity, Salt Resistance, Antibiofilm Properties and Their Membrane-Disruptive Mechanism

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.