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

摘要

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.