Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
Oktawian Stachurski,
Damian Neubauer,
Aleksandra Walewska,
Emilia Iłowska,
Marta Bauer,
Sylwia Bartoszewska,
Karol Sikora,
Aleksandra Hać,
Dariusz Wyrzykowski,
Adam Prahl,
Wojciech Kamysz,
Emilia Sikorska
Affiliations
Oktawian Stachurski
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
Damian Neubauer
Faculty of Pharmacy, Medicinal University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland
Aleksandra Walewska
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
Emilia Iłowska
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
Marta Bauer
Faculty of Pharmacy, Medicinal University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland
Sylwia Bartoszewska
Faculty of Pharmacy, Medicinal University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland
Karol Sikora
Faculty of Pharmacy, Medicinal University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland
Aleksandra Hać
Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland
Dariusz Wyrzykowski
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
Adam Prahl
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
Wojciech Kamysz
Faculty of Pharmacy, Medicinal University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland
Emilia Sikorska
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C12-C18 fatty acids attached to the N-terminal part of the peptides. The findings were discussed in the context of the relationship among biological activity, self-assembly, stability, and membrane interactions. All the lipopeptides showed the ability to self-assemble in PBS solution. In most cases, the critical aggregation concentration (CAC) much surpassed the minimal inhibitory concentration (MIC) values, suggesting that monomers are the main active form of lipopeptides. The introduction of β-alanine into the peptide sequence resulted in a compound with a high propensity to fibrillate, which increased the peptide stability and activity against S. epidermidis and C. albicans and reduced the cytotoxicity against human keratinocytes. The results of our study indicated that the target of action of lipopeptides is the bacterial membrane. Interestingly, the type of peptide counterion may affect the degree of penetration of the lipid bilayer. In addition, the binding of the lipopeptide to the membrane of Gram-negative bacteria may lead to the release of calcium ions necessary for stabilization of the lipopolysaccharide layer.