LAUSR

Antimicrobial polypeptides are promising mimics of antimicrobial peptides (AMPs) with low risks of antimicrobial resistance (AMR). Polypeptides with facile and efficient production, high antimicrobial activity, and low toxicity toward mammalian cells are highly desirable for practical applications. Herein, triblock copolypeptides with chloro groups (PPGn-PCPBLGm) and different main-chain lengths were synthesized via an ultrafast ring-opening polymerization (ROP) using a macroinitiator, namely poly(propylene glycol) bis(2-aminopropyl ether), and purified or nonpurified monomer (i.e., CPBLG-NCA). PPGn-PCPBLGm with 90 amino acid residues can be readily prepared within 300 s. Imidazolium-based block copolypeptides (PPGn-PILm) were facilely prepared via nucleophilic substitution of PPGn-PCPBLGm with NaN3 and subsequent "click" chemistry. α-Helical PPGn-PILm can self-assemble into nanostructured and cationic micelles which displayed highly potent antimicrobial activity and low hemolysis. The top-performing material, namely PPG34-PIL70, showed low minimum inhibitory concentration (MIC) against both Gram-positive S. aureus and Gram-negative E. coli (25 μg mL-1). It also displayed low toxicity against mouse embryonic fibroblast (NIH 3T3) and human embryonic kidney (293T) cells at 2× MIC.