Highly efficient antibacterial diblock copolypeptides based on lysine and phenylalanine

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Microbiology

Background:

• Growing antibiotic resistance necessitates the development of novel antimicrobial agents.
• Antimicrobial peptides (AMPs) are a promising class of therapeutics with broad-spectrum activity.
• Synthetic AMPs offer advantages in terms of stability and tunability compared to natural AMPs.

Purpose of the Study:

• To synthesize and characterize amphiphilic diblock copolypeptides.
• To evaluate the antibacterial efficacy and mechanism of action of these novel copolypeptides.
• To assess the selectivity of the copolypeptides towards bacterial cells versus mammalian cells.

Main Methods:

• Synthesis of diblock copolypeptides (K30-b-F15, K30-b-F30, K30-b-F45) via N-carboxy-α-amino-anhydride ring-opening polymerization.
• Determination of minimum inhibitory concentrations (MICs) against *Escherichia coli* (Gram-negative) and *Staphylococcus aureus* (Gram-positive).
• Investigation of bacterial morphological changes using transmission electron microscopy (TEM) and laser scanning confocal microscopy (LSCM).
• Assessment of cytotoxicity using CCK-8 assays.

Main Results:

• Synthesized copolypeptides demonstrated excellent antibacterial efficacy against both Gram-positive and Gram-negative bacteria.
• MIC values were found to be 8 μg/mL for *E. coli* and 2 μg/mL for *S. aureus*, outperforming many existing AMPs.
• TEM and LSCM revealed a pore-forming mechanism similar to natural cationic peptides.
• High selectivity for bacterial cells over mammalian cells was observed, indicated by CCK-8 assays and MIC values.

Conclusions:

• Amphiphilic diblock copolypeptides exhibit potent and selective antibacterial activity.
• The pore-forming mechanism contributes to their efficacy against a broad spectrum of bacteria.
• These novel copolypeptides represent promising candidates for the development of next-generation antibiotics.