A Novel Trp-rich Model Antimicrobial Peptoid with Increased Protease Stability

In order to increase protease stability of a novel Trp-rich model antimicrobial peptide, K₆L₂W₃ (KLWKKWKKWLK- NH₂ )and investigate the effect of L-amino acid to peptoid residue conversion on biological functions, we synthesized its antimicrobial peptoid, k₆l₂w₃ . Peptoid k₆l₂w₃ had similar bacterial selectivity compared to peptide k₆6L₂W₃ . The bactericidal rate of k₆l₂w₃ was somewhat slower than that of K₆L₂W₃ . Peptoid k₆l₂w₃ exhibited very little dye leakage from bacterial outer-membrane mimicking PE/PG liposomes, as observed in K₆L₂W₃ , indicating that the major target site of K₆L₂W₃ and k₆l₂w₃ may be not the cell membrane but the cytoplasm of bacteria. Trypsin treatment of K₆L₂W₃ completely abolished antimicrobial activities against Escherichia coli and Staphylococcus aureus. In contrast, the antimicrobial activity of k₆l₂w₃ was completely preserved after trypsin treatment. Taken together, our results suggested that antimicrobial peptoid k₆l₂w₃ can potentially serves as a promising therapeutic agent for the treatment of microbial infection.