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

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Author(s)

  • Sam Clark
  • Curtis Dobson
  • Lynda Harris
  • Christopher Knight
  • Thomas Jowitt

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Publication details

JournalCommunication Biology
DateAccepted/In press - 29 Mar 2021
DatePublished (current) - 21 May 2021
Issue number605
Volume4
Original languageEnglish

Abstract

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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© The Author(s) 2021

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