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

• Published in: International Journal of Molecular Sciences
• Main Authors: Ida K. Ø. Hansen, Tomas Lövdahl, Danijela Simonovic, Kine Ø. Hansen, Aaron J. C. Andersen, Hege Devold, Céline S. M. Richard, Jeanette H. Andersen, Morten B. Strøm, Tor Haug
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2020
• Subjects: Arctic; ascidian; antimicrobial; synthetic; peptide; Synoicum turgens; Biology (General); QH301-705.5; Chemistry; QD1-999
• Online Access: https://doi.org/10.3390/ijms21155460; https://doaj.org/article/571f098cccc94f44a4be8cdbb2b6dc26

Turgencin A, a potent antimicrobial peptide isolated from the Arctic sea squirt Synoicum turgens , 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 StAMP-9 displayed bactericidal activity, with minimal inhibitory concentrations of 7.8 µg/mL against Staphylococcus aureus and 3.9 µg/mL against Escherichia coli , and no cytotoxic effects against mammalian cells. Preliminary experiments indicate the bacterial membranes as immediate and primary targets.