Dey, Hymonti;
Simonovic, Danijela;
Norberg-Schulz Hagen, Ingrid;
Vasskog, Terje;
Fredheim, Elizabeth G. Aarag;
Blencke, Hans-Matti;
Anderssen, Trude;
Strøm, Morten B.;
Haug, Tor
Synthesis and Antimicrobial Activity of Short Analogues of the Marine Antimicrobial Peptide Turgencin A: Effects of SAR Optimizations, Cys-Cys Cyclization and Lipopeptide Modifications
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Media type:
E-Article
Title:
Synthesis and Antimicrobial Activity of Short Analogues of the Marine Antimicrobial Peptide Turgencin A: Effects of SAR Optimizations, Cys-Cys Cyclization and Lipopeptide Modifications
Contributor:
Dey, Hymonti;
Simonovic, Danijela;
Norberg-Schulz Hagen, Ingrid;
Vasskog, Terje;
Fredheim, Elizabeth G. Aarag;
Blencke, Hans-Matti;
Anderssen, Trude;
Strøm, Morten B.;
Haug, Tor
imprint:
MDPI AG, 2022
Published in:International Journal of Molecular Sciences
Description:
<jats:p>We have synthesised short analogues of the marine antimicrobial peptide Turgencin A from the colonial Arctic ascidian Synoicum turgens. In this study, we focused on a central, cationic 12-residue Cys-Cys loop region within the sequence. Modified (tryptophan- and arginine-enriched) linear peptides were compared with Cys-Cys cyclic derivatives, and both linear and Cys-cyclic peptides were N-terminally acylated with octanoic acid (C8), decanoic acid (C10) or dodecanoic acid (C12). The highest antimicrobial potency was achieved by introducing dodecanoic acid to a cyclic Turgencin A analogue with low intrinsic hydrophobicity, and by introducing octanoic acid to a cyclic analogue displaying a higher intrinsic hydrophobicity. Among all tested synthetic Turgencin A lipopeptide analogues, the most promising candidates regarding both antimicrobial and haemolytic activity were C12-cTurg-1 and C8-cTurg-2. These optimized cyclic lipopeptides displayed minimum inhibitory concentrations of 4 µg/mL against Staphylococcus aureus, Escherichia coli and the fungus Rhodothorula sp. Mode of action studies on bacteria showed a rapid membrane disruption and bactericidal effect of the cyclic lipopeptides. Haemolytic activity against human erythrocytes was low, indicating favorable selective targeting of bacterial cells.</jats:p>