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Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis

Ultrashort cationic lipopeptides (USCLs) are promising antimicrobial agents that hypothetically may be alternatively used to combat pathogens such as bacteria and fungi. In general, USCLs consist of fatty acid chains and a few basic amino acid residues. The main shortcoming of USCLs is their relativ...

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Autores principales: Neubauer, Damian, Jaśkiewicz, Maciej, Bauer, Marta, Gołacki, Krzysztof, Kamysz, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024302/
https://www.ncbi.nlm.nih.gov/pubmed/31936341
http://dx.doi.org/10.3390/molecules25020257
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author Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Gołacki, Krzysztof
Kamysz, Wojciech
author_facet Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Gołacki, Krzysztof
Kamysz, Wojciech
author_sort Neubauer, Damian
collection PubMed
description Ultrashort cationic lipopeptides (USCLs) are promising antimicrobial agents that hypothetically may be alternatively used to combat pathogens such as bacteria and fungi. In general, USCLs consist of fatty acid chains and a few basic amino acid residues. The main shortcoming of USCLs is their relatively high cytotoxicity and hemolytic activity. This study focuses on the impact of the hydrophobic fatty acid chain, on both antimicrobial and hemolytic activities. To learn more about this region, a series of USCLs with different straight-chain fatty acids (C8, C10, C12, C14) attached to the tripeptide with two arginine residues were synthesized. The amino acid at the N-terminal position was exchanged for proteinogenic and non-proteinogenic amino acid residues (24 in total). Moreover, the branched fatty acid residues were conjugated to N-terminus of a dipeptide with two arginine residues. All USCLs had C-terminal amides. USCLs were tested against reference bacterial strains (including ESKAPE group) and Candida albicans. The hemolytic potential was tested on human erythrocytes. Hydrophobicity of the compounds was evaluated by RP-HPLC. Shortening of the fatty acid chain and simultaneous addition of amino acid residue at N-terminus were expected to result in more selective and active compounds than those of the reference lipopeptides with similar lipophilicity. Hypothetically, this approach would also be beneficial to other antimicrobial peptides where N-lipidation strategy was used to improve their biological characteristics.
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spelling pubmed-70243022020-03-11 Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis Neubauer, Damian Jaśkiewicz, Maciej Bauer, Marta Gołacki, Krzysztof Kamysz, Wojciech Molecules Article Ultrashort cationic lipopeptides (USCLs) are promising antimicrobial agents that hypothetically may be alternatively used to combat pathogens such as bacteria and fungi. In general, USCLs consist of fatty acid chains and a few basic amino acid residues. The main shortcoming of USCLs is their relatively high cytotoxicity and hemolytic activity. This study focuses on the impact of the hydrophobic fatty acid chain, on both antimicrobial and hemolytic activities. To learn more about this region, a series of USCLs with different straight-chain fatty acids (C8, C10, C12, C14) attached to the tripeptide with two arginine residues were synthesized. The amino acid at the N-terminal position was exchanged for proteinogenic and non-proteinogenic amino acid residues (24 in total). Moreover, the branched fatty acid residues were conjugated to N-terminus of a dipeptide with two arginine residues. All USCLs had C-terminal amides. USCLs were tested against reference bacterial strains (including ESKAPE group) and Candida albicans. The hemolytic potential was tested on human erythrocytes. Hydrophobicity of the compounds was evaluated by RP-HPLC. Shortening of the fatty acid chain and simultaneous addition of amino acid residue at N-terminus were expected to result in more selective and active compounds than those of the reference lipopeptides with similar lipophilicity. Hypothetically, this approach would also be beneficial to other antimicrobial peptides where N-lipidation strategy was used to improve their biological characteristics. MDPI 2020-01-08 /pmc/articles/PMC7024302/ /pubmed/31936341 http://dx.doi.org/10.3390/molecules25020257 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Gołacki, Krzysztof
Kamysz, Wojciech
Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title_full Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title_fullStr Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title_full_unstemmed Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title_short Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
title_sort ultrashort cationic lipopeptides–effect of n-terminal amino acid and fatty acid type on antimicrobial activity and hemolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024302/
https://www.ncbi.nlm.nih.gov/pubmed/31936341
http://dx.doi.org/10.3390/molecules25020257
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