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Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics

This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C(12)-C(18) 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 m...

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Autores principales: Stachurski, Oktawian, Neubauer, Damian, Walewska, Aleksandra, Iłowska, Emilia, Bauer, Marta, Bartoszewska, Sylwia, Sikora, Karol, Hać, Aleksandra, Wyrzykowski, Dariusz, Prahl, Adam, Kamysz, Wojciech, Sikorska, Emilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686977/
https://www.ncbi.nlm.nih.gov/pubmed/36358146
http://dx.doi.org/10.3390/antibiotics11111491
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author Stachurski, Oktawian
Neubauer, Damian
Walewska, Aleksandra
Iłowska, Emilia
Bauer, Marta
Bartoszewska, Sylwia
Sikora, Karol
Hać, Aleksandra
Wyrzykowski, Dariusz
Prahl, Adam
Kamysz, Wojciech
Sikorska, Emilia
author_facet Stachurski, Oktawian
Neubauer, Damian
Walewska, Aleksandra
Iłowska, Emilia
Bauer, Marta
Bartoszewska, Sylwia
Sikora, Karol
Hać, Aleksandra
Wyrzykowski, Dariusz
Prahl, Adam
Kamysz, Wojciech
Sikorska, Emilia
author_sort Stachurski, Oktawian
collection PubMed
description This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C(12)-C(18) 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.
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spelling pubmed-96869772022-11-25 Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics Stachurski, Oktawian Neubauer, Damian Walewska, Aleksandra Iłowska, Emilia Bauer, Marta Bartoszewska, Sylwia Sikora, Karol Hać, Aleksandra Wyrzykowski, Dariusz Prahl, Adam Kamysz, Wojciech Sikorska, Emilia Antibiotics (Basel) Article This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C(12)-C(18) 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. MDPI 2022-10-27 /pmc/articles/PMC9686977/ /pubmed/36358146 http://dx.doi.org/10.3390/antibiotics11111491 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stachurski, Oktawian
Neubauer, Damian
Walewska, Aleksandra
Iłowska, Emilia
Bauer, Marta
Bartoszewska, Sylwia
Sikora, Karol
Hać, Aleksandra
Wyrzykowski, Dariusz
Prahl, Adam
Kamysz, Wojciech
Sikorska, Emilia
Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title_full Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title_fullStr Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title_full_unstemmed Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title_short Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
title_sort understanding the role of self-assembly and interaction with biological membranes of short cationic lipopeptides in the effective design of new antibiotics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686977/
https://www.ncbi.nlm.nih.gov/pubmed/36358146
http://dx.doi.org/10.3390/antibiotics11111491
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