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The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences

Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to th...

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Autores principales: Clark, Sam, Jowitt, Thomas A., Harris, Lynda K., Knight, Christopher G., Dobson, Curtis B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140080/
https://www.ncbi.nlm.nih.gov/pubmed/34021253
http://dx.doi.org/10.1038/s42003-021-02137-7
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author Clark, Sam
Jowitt, Thomas A.
Harris, Lynda K.
Knight, Christopher G.
Dobson, Curtis B.
author_facet Clark, Sam
Jowitt, Thomas A.
Harris, Lynda K.
Knight, Christopher G.
Dobson, Curtis B.
author_sort Clark, Sam
collection PubMed
description Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity. We found the shortest active peptides were 4 or 5 residues in length, and the overall landscapes of activity against gram-positive and gram-negative bacteria and a yeast were positively correlated. For all three organisms we found a single activity peak corresponding to sequences with around 40% R; the presence of adjacent W duplets and triplets also conferred greater activity. The mechanistic basis of these activities comprises a combination of lipid binding, particularly to negatively charged membranes, and additionally peptide aggregation, a mode of action previously uninvestigated for such peptides. The maximum specific antimicrobial activity appeared to occur in peptides of around 10 residues, suggesting ‘diminishing returns’ for developing larger peptides, when activity is considered per residue of peptide.
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spelling pubmed-81400802021-06-03 The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences Clark, Sam Jowitt, Thomas A. Harris, Lynda K. Knight, Christopher G. Dobson, Curtis B. Commun Biol Article Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity. We found the shortest active peptides were 4 or 5 residues in length, and the overall landscapes of activity against gram-positive and gram-negative bacteria and a yeast were positively correlated. For all three organisms we found a single activity peak corresponding to sequences with around 40% R; the presence of adjacent W duplets and triplets also conferred greater activity. The mechanistic basis of these activities comprises a combination of lipid binding, particularly to negatively charged membranes, and additionally peptide aggregation, a mode of action previously uninvestigated for such peptides. The maximum specific antimicrobial activity appeared to occur in peptides of around 10 residues, suggesting ‘diminishing returns’ for developing larger peptides, when activity is considered per residue of peptide. Nature Publishing Group UK 2021-05-21 /pmc/articles/PMC8140080/ /pubmed/34021253 http://dx.doi.org/10.1038/s42003-021-02137-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Clark, Sam
Jowitt, Thomas A.
Harris, Lynda K.
Knight, Christopher G.
Dobson, Curtis B.
The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title_full The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title_fullStr The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title_full_unstemmed The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title_short The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
title_sort lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140080/
https://www.ncbi.nlm.nih.gov/pubmed/34021253
http://dx.doi.org/10.1038/s42003-021-02137-7
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