Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity

Amanda L. Russell, Anthony M. Kennedy, Anne M. Spuches, Divakaramenon Venugopal, Jayendra B. Bhonsle, Rickey P. Hicks

Research output: Contribution to journalArticle

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Abstract

In our laboratory we developed a series of antimicrobial peptides that exhibit selectivity and potency for prokaryotic over eukaryotic cells (Hicks et al., 2007). Circular dichroism (CD), isothermal calorimetry (ITC) and calcein leakage assays were conducted to determine the mechanism of lipid binding of a representative peptide 1 (Ac-GF-Tic-Oic-GK-Tic-Oic-GF-Tic-Oic-GK-Tic-KKKK- CONH2) to model membranes. POPC liposomes were used as a simple model for eukaryotic membranes and 4:1 POPC:POPG liposomes were used as a simple model for prokaryotic membranes. CD, ITC and calcein leakage data clearly indicate that compound 1 interacts via very different mechanisms with the two different liposome membranes. Compound 1 exhibits weaker binding and induces less calcein leakage in POPC liposomes than POPC:POPG (4:1 mole ratio) liposomes. The predominant binding mechanism to POPC appears to be limited to surface interactions while the mechanism of binding to 4:1 POPC:POPG most likely involves some type of pore formation.

Original languageEnglish (US)
Pages (from-to)488-497
Number of pages10
JournalChemistry and Physics of Lipids
Volume163
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Antimicrobial peptide
  • Calcein fluorescence leakage
  • Circular dichroism
  • Isothermal titration calorimetry
  • Liposomes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this

Russell, A. L., Kennedy, A. M., Spuches, A. M., Venugopal, D., Bhonsle, J. B., & Hicks, R. P. (2010). Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity. Chemistry and Physics of Lipids, 163(6), 488-497. https://doi.org/10.1016/j.chemphyslip.2010.03.009