Boosting Antimicrobial Peptides by Hydrophobic Oligopeptide End Tags

Research output: Contribution to journalArticle

Abstract

A novel approach for boosting antimicrobial peptides through end tagging with hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17), tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungal Candida albicans. Microbicidal potency increased with tag length, also in plasma, and was larger for Trp and Phe stretches than for aliphatic ones. The enhanced microbicidal effects correlated to a higher degree of bacterial wall rupture. Analogously, tagging promoted peptide binding to model phospholipid membranes and liposome rupture, particularly for anionic and cholesterol-void membranes. Tagged peptides displayed low toxicity, particularly in the presence of serum, and resisted degradation by human leukocyte elastase and by staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo and in vivo in porcine S. aureus skin infection models. The generality of end tagging for facile boosting of antimicrobial peptides without the need for post-synthesis modification was also demonstrated.

Details

Authors
  • Artur Schmidtchen
  • Mukesh Pasupuleti
  • Matthias Mörgelin
  • Mina Davoudi
  • Jan Alenfall
  • Anna Chalupka
  • Martin Malmsten
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine
  • Dermatology and Venereal Diseases
Original languageEnglish
Pages (from-to)17584-17594
JournalJournal of Biological Chemistry
Volume284
Issue number26
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Pasupuleti, M., 2009, Department of Clinical Sciences, Lund University. 198 p.

Research output: ThesisDoctoral Thesis (compilation)

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