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Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers

Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic N-terminal amino acid in USCLs result in compounds wit...

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Autores principales: Neubauer, Damian, Jaśkiewicz, Maciej, Bauer, Marta, Olejniczak-Kęder, Agata, Sikorska, Emilia, Sikora, Karol, Kamysz, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036666/
https://www.ncbi.nlm.nih.gov/pubmed/33804887
http://dx.doi.org/10.3390/ijms22073299
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author Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Olejniczak-Kęder, Agata
Sikorska, Emilia
Sikora, Karol
Kamysz, Wojciech
author_facet Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Olejniczak-Kęder, Agata
Sikorska, Emilia
Sikora, Karol
Kamysz, Wojciech
author_sort Neubauer, Damian
collection PubMed
description Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic N-terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. l-cystine diamide and l-lysine amide linkers were used as spacers. Antimicrobial activity against planktonic and biofilm cultures of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) strains and Candida sp. as well as hemolytic and cytotoxic activities were examined. Moreover, antimicrobial activity in the presence of human serum and the ability to form micelles were evaluated. Membrane permeabilization study, serum stability assay, and molecular dynamics were performed. Generally, critical aggregation concentration was linearly correlated with hydrophobicity. Gemini surfactants were more active than the parent USCLs, and they turned out to be selective antimicrobial agents with relatively low hemolytic and cytotoxic activities. Geminis with the l-cystine diamide spacer seem to be less cytotoxic than their l-lysine amide counterparts, but they exhibited lower antibiofilm and antimicrobial activities in serum. In some cases, geminis with branched fatty acid chains and N-terminal hydrophobic amino acid resides exhibited enhanced selectivity to pathogens over human cells.
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spelling pubmed-80366662021-04-12 Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers Neubauer, Damian Jaśkiewicz, Maciej Bauer, Marta Olejniczak-Kęder, Agata Sikorska, Emilia Sikora, Karol Kamysz, Wojciech Int J Mol Sci Article Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic N-terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. l-cystine diamide and l-lysine amide linkers were used as spacers. Antimicrobial activity against planktonic and biofilm cultures of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) strains and Candida sp. as well as hemolytic and cytotoxic activities were examined. Moreover, antimicrobial activity in the presence of human serum and the ability to form micelles were evaluated. Membrane permeabilization study, serum stability assay, and molecular dynamics were performed. Generally, critical aggregation concentration was linearly correlated with hydrophobicity. Gemini surfactants were more active than the parent USCLs, and they turned out to be selective antimicrobial agents with relatively low hemolytic and cytotoxic activities. Geminis with the l-cystine diamide spacer seem to be less cytotoxic than their l-lysine amide counterparts, but they exhibited lower antibiofilm and antimicrobial activities in serum. In some cases, geminis with branched fatty acid chains and N-terminal hydrophobic amino acid resides exhibited enhanced selectivity to pathogens over human cells. MDPI 2021-03-24 /pmc/articles/PMC8036666/ /pubmed/33804887 http://dx.doi.org/10.3390/ijms22073299 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Neubauer, Damian
Jaśkiewicz, Maciej
Bauer, Marta
Olejniczak-Kęder, Agata
Sikorska, Emilia
Sikora, Karol
Kamysz, Wojciech
Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title_full Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title_fullStr Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title_full_unstemmed Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title_short Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers
title_sort biological and physico-chemical characteristics of arginine-rich peptide gemini surfactants with lysine and cystine spacers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036666/
https://www.ncbi.nlm.nih.gov/pubmed/33804887
http://dx.doi.org/10.3390/ijms22073299
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