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Direct comparison of membrane interactions of model peptides composed of only Leu and Lys residues.
- Source :
-
Biopolymers [Biopolymers] 2003; Vol. 71 (1), pp. 2-16. - Publication Year :
- 2003
-
Abstract
- We compared the properties of two peptides of identical size and amino acid composition, Ac-(LKKL)(5)-NHEt and Ac-(KL)(10)-NHEt. Both are amphipathic, but only Ac-(LKKL)(5)-NHEt is a potent promoter of negative curvature. CD studies performed in the presence of lipids confirmed that under these conditions Ac-(LKKL)(5)-NHEt forms an alpha-helix, and Ac-(KL)(10)-NHEt adopts a beta structure. We studied their binding affinity by centrifugation and isothermal titration calorimetry techniques. The Ac-(LKKL)(5)-NHEt bound to zwitterionic and anionic liposomes, while Ac-(KL)(10)-NHEt interacted mainly with anionic liposomes. Ac-(LKKL)(5)-NHEt was more lytic than Ac-(KL)(10)-NHEt for zwitterionic palmitoyloleoylphosphatidylcholine (POPC) liposomes, and for liposomes composed of lipids extracted from either sheep or human erythrocytes (RBC). Both peptides had similar lytic and lipid mixing activities for liposomes containing anionic lipids. Both peptides were highly hemolytic, with Ac-(LKKL)(5)-NHEt active against sheep RBC and Ac-(KL)(10)-NHEt more active against human RBC. From their respective minimal effective concentrations (MECs) as antimicrobial agents, we judged Ac-(KL)(10)-NHEt to be 2 to 5-fold more potent than Ac-(LKKL)(5)-NHEt in media that contained physiological concentrations of NaCl. Notwithstanding, both peptides had MECs <1 microg/mL for Escherichia coli and Pseudomonas aeruginosa and <4 microg/mL for Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. Although selectivity of antimicrobial peptides for bacterial membranes may result, in part, from the preferential display of anionic residues in these membranes, inability to interact with or bind to zwitterionic phospholipids offers no guarantee that the peptide will lack appreciable cytotoxicity for host cells.<br /> (Copyright 2003 Wiley Periodicals, Inc.)
- Subjects :
- Anti-Infective Agents chemistry
Anti-Infective Agents pharmacology
Calorimetry, Differential Scanning
Circular Dichroism
Hemolysis drug effects
Humans
Membrane Fusion
Membranes, Artificial
Models, Biological
Oligopeptides chemical synthesis
Oligopeptides pharmacology
Peptides chemical synthesis
Protein Structure, Secondary
Leucine
Liposomes chemistry
Lysine
Oligopeptides chemistry
Peptides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3525
- Volume :
- 71
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biopolymers
- Publication Type :
- Academic Journal
- Accession number :
- 12712497
- Full Text :
- https://doi.org/10.1002/bip.10372