Synthetic Polypeptides with Cationic Arginine Moieties Showing High Antimicrobial Activity in Similar Mineral Environments to Blood Plasma

Abstract

Translocation of cell-penetrating peptides is promoted by incorporated arginine or other guanidinium groups. However, relatively little research has considered the role of these functional groups on antimicrobial peptide activity. A series of cationic linear-, star- and multi-branched-poly(L-arginine-co-L-phenylalanine) have been synthesized via the ring-opening copolymerizations of corresponding N-carboxyanhydride monomers followed by further modifications using the N-heterocyclic carbene organocatalyst. All the polymers are characterized by the random coiled microstructure. Antibacterial efficacy, tested by the gram-positive B. subtilis bacteria and the gram-negative E. coli bacteria, was sensitive to the structure and relative composition of the copolymer and increased in the order of linear- L-arginine)23-co-(L-phenylalanine)7]8 polymer showed the best antibacterial property with the lowest minimum inhibitory concentration values of 48 μg mL−1 for E. coli and 32 μg mL−1 for B. subtilis. The efficacy was prominent for B. subtilis due to the anionic nature of its membrane. All of the resultant arginine moiety-containing polypeptides showed excellent blood compatibility. The antibiotic effect of the copolymers with arginine moieties was retained even in the environment bearing Ca2+, Mg2+, and Na+ ions similar to blood plasma. The cationic arginine-bearing copolypeptides were also effective for the sterilization of naturally occurring sources of water such as lakes, seas, rain, and sewage, showing a promising range of applicability.

Keywords

• amino acids
• antimicrobial peptides
• arginine
• <i>N</i>-carboxyanhydrides
• polypeptides
• ring-opening polymerization