Antimicrobial activity of small synthetic peptides based on the marine peptide turgencin A: Prediction of antimicrobial peptide sequences in a natural peptide and strategy for optimization of potency

Abstract

Turgencin A, a potent antimicrobial peptide isolated from the Arctic sea squirt <i>Synoicum turgens</i>, consists of 36 amino acid residues and three disulfide bridges, making it challenging to synthesize. The aim of the present study was to develop a truncated peptide with an antimicrobial drug lead potential based on turgencin A. The experiments consisted of: (1) sequence analysis and prediction of antimicrobial potential of truncated 10-mer sequences; (2) synthesis and antimicrobial screening of a lead peptide devoid of the cysteine residues; (3) optimization of in vitro antimicrobial activity of the lead peptide using an amino acid replacement strategy; and (4) screening the synthesized peptides for cytotoxic activities. In silico analysis of turgencin A using various prediction software indicated an internal, cationic 10-mer sequence to be putatively antimicrobial. The synthesized truncated lead peptide displayed weak antimicrobial activity. However, by following a systematic amino acid replacement strategy, a modified peptide was developed that retained the potency of the original peptide. The optimized peptide <b>StAMP-9</b> displayed bactericidal activity, with minimal inhibitory concentrations of 7.8 µg/mL against <i>Staphylococcus aureus</i> and 3.9 µg/mL against <i>Escherichia coli</i>, and no cytotoxic effects against mammalian cells. Preliminary experiments indicate the bacterial membranes as immediate and primary targets.