Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity.
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-CONH(2)) 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.
Russell
Amanda L
AL
Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA.
Kennedy
Anthony M
AM
Spuches
Anne M
AM
Venugopal
Divakaramenon
D
Bhonsle
Jayendra B
JB
Hicks
Rickey P
RP
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002151:Calorimetry; D002942:Circular Dichroism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D013816:Thermodynamics
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine