Modulating the activity of membrane-active peptides through Zn(II) complexation

Pierre Alexandre Paquet-Côté, Kellie L. Tuck, Jean Philippe Paradis, Bim Graham, Normand Voyer

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Seeking to increase the selectivity of antimicrobial peptides for prokaryotic cells, we incorporated a bis-dipicolyl amine (bis-DPA) ligand at the N-terminus of de novo designed model peptides. The Zn2·bisDPA complex increases the interaction of peptides with anionic model membranes, while decreasing interactions with zwitterionic model membranes. Further, it improves the peptides’ antimicrobial activity and decreases their hemolytic activity without substantial changes to their secondary structure. Therefore, incorporating a Zn2·bisDPA complex is a useful strategy to enhance the selectivity of antimicrobial peptides.

Original languageEnglish
Pages (from-to)4672-4676
Number of pages5
JournalTetrahedron Letters
Issue number50
Publication statusPublished - 13 Dec 2017


  • Antimicrobial activity
  • Hemolytic activity
  • Membrane-active peptides
  • Secondary structure
  • Zinc-dipicolylamine complex

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