Structure-activity relationships for the β-hairpin cationic antimicrobial peptide polyphemusin I

Jon Paul S. Powers, Annett Rozek, Robert E.W. Hancock

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65 Citations (Scopus)


The solution structure of polyphemusin I was determined using 1H-NMR spectroscopy. Polyphemusin I was found to be an amphipathic, β-hairpin connected by a type I′ β-turn. The 17 low-energy structures aligned very well over the β-sheet region while both termini were poorly defined due in part to a hinge-like region centred in the molecule about arginine residues 6 and 16. Conversely, a linear analogue, PM1-S, with all cysteines simultaneously replaced with serine was found to be dynamic in nature, and a lack of medium and long-range NOEs indicated that this molecule displayed no favoured conformation. Circular dichroism (CD) spectroscopy confirmed that in solution, 50% trifluoroethanol (TFE) and in the presence of liposomes, PM1-S remained unstructured. The antimicrobial activity of PM1-S was found to be 4- to 16-fold less than that of polyphemusin I and corresponded with a 4-fold reduction in bacterial membrane depolarization. Both peptides were able to associate with lipid bilayers in a similar fashion; however, PM1-S was completely unable to translocate model membranes while polyphemusin I retained this activity. It was concluded that the disulfide-constrained, β-sheet structure of polyphemusin I is required for maximum antimicrobial activity. Disruption of this structure results in reduced antimicrobial activity and completely abolishes membrane translocation indicating that the linear PM1-S acts through a different antimicrobial mechanism.

Original languageEnglish
Pages (from-to)239-250
Number of pages12
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number2
Publication statusPublished or Issued - 6 May 2004
Externally publishedYes


  • Antimicrobial peptide
  • CD
  • DO
  • MHC
  • MIC
  • NMR
  • Nuclear magnetic resonance
  • Polyphemusin I
  • circular dichroism
  • deuterium oxide
  • minimal haemolytic concentration
  • minimal inhibitory concentration
  • nuclear magnetic resonance
  • β-Sheet

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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