1. Interaction of Gramicidin S and its Aromatic Amino-Acid Analog with Phospholipid Membranes
- Author
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Robert S. Hodges, Masoud Jelokhani-Niaraki, Laura Wheaton, Una E. Hassenstein, and Joseph E. Meissner
- Subjects
Biophysics ,Gramicidin S ,Calorimetry ,Hemolysis ,7. Clean energy ,01 natural sciences ,Protein Structure, Secondary ,Amino Acids, Aromatic ,03 medical and health sciences ,chemistry.chemical_compound ,Anti-Infective Agents ,Fluorescence Resonance Energy Transfer ,Animals ,Organic chemistry ,Amino Acid Sequence ,Lipid bilayer ,POPC ,Phospholipids ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Membranes ,010405 organic chemistry ,Chemistry ,Circular Dichroism ,Vesicle ,Cell Membrane ,Gramicidin ,Biological membrane ,Isothermal titration calorimetry ,Cyclic peptide ,0104 chemical sciences ,Crystallography ,Antimicrobial Cationic Peptides - Abstract
To investigate the mechanism of interaction of gramicidin S-like antimicrobial peptides with biological membranes, a series of five decameric cyclic cationic beta-sheet-beta-turn peptides with all possible combinations of aromatic D-amino acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar identical with Phe, Tyr, Trp), were synthesized. Conformations of these cyclic peptides were comparable in aqueous solutions and lipid vesicles. Isothermal titration calorimetry measurements revealed entropy-driven binding of cyclic peptides to POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems was endothermic-exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs with exothermic binding to POPC vesicles. Application of one- and two-site binding (partitioning) models to binding isotherms of exothermic and endothermic binding processes, respectively, resulted in determination of peptide-lipid membrane binding constants (K(b)). The K(b1) and K(b2) values for endothermic two-step binding processes corresponded to high and low binding affinities (K(b1) >or= 100 K(b2)). Conformational change of cyclic peptides in transferring from buffer to lipid bilayer surfaces was estimated using fluorescence resonance energy transfer between the Tyr-Trp pair in one of the peptide constructs. The cyclic peptide conformation expands upon adsorption on lipid bilayer surface and interacts more deeply with the outer monolayer causing bilayer deformation, which may lead to formation of nonspecific transient peptide-lipid porelike zones causing membrane lysis.
- Published
- 2008
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