Short Antimicrobial Peptides Exhibiting Antibacterial and Anti‐Inflammatory Activities Derived from the N‐Terminal Helix of Papiliocin

Papiliocin is a 37‐residue antimicrobial peptide, with Trp2 and Phe5 previously reported as key residues necessary for its antibacterial activity. This study determined the essential length of the N‐terminal fragment of papiliocin necessary to retain its biological activity. We designed and synthesized an array of seven peptides from the N‐terminal helix ( PapN ), with longest peptide with 22 residues and the shortest peptide consisting of the first 10 residues. The minimum inhibitory concentration ( MIC ) values and cytotoxicity measurement revealed that a PapN ‐12mer containing a three‐turn, amphipathic helix was the shortest peptide exhibiting antibacterial activity without cytotoxicity. Additionally, PapN ‐20mer peptide containing two isoleucines at the C‐terminus represented the shortest peptide exhibiting potent anti‐inflammatory activities by inhibiting nitric oxide production and inflammatory cytokine production in lipopolysaccharide‐stimulated mouse macrophage RAW264 .7 cells. These results provided valuable insights into the design of short, potent peptide analogs of papiliocin.