Tailoring the Physicochemical Properties of Antimicrobial Peptides onto a Thiazole-Based γ‑Peptide Foldamer

Antimicrobial
peptides (AMPs) are amphipathic molecules displaying
broad-spectrum bactericidal activity, providing opportunities to develop
a new generation of antibiotics. However, their use is limited either
by poor metabolic stability or by high hemolytic activity. We herein
addressed the potential of thiazole-based γ-peptide oligomers
named ATCs as tunable scaffolds to design polycationic AMP mimetics.
Knowing the side chain distribution along the backbone, we rationally
designed facially amphiphilic sequences with bactericidal effect in
the micromolar range. Since no hemolytic activity was detected up
to 100 μM, this class of compounds has shown the potential for
therapeutic development.