Investigating the structural impact of the antimicrobial peptide combi-2 in model membranes
The hexapeptide FRWWHR (combi-2) was identified by combinatorial chemistry methods. This peptide is a cationic antimicrobial peptide with a broad spectrum of activity against both Gram Positive (Gram+) and Gram Negative (Gram–). Very few studies have been devoted to its interaction with complex model membranes. The objective of this project is to investigate the impact of the antimicrobial peptide combi-2 in model membranes using Fourier Transform infrared (FTIR), fluorescence, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and atomic force microscopy (AFM) techniques. The first specific aim is to determine the influence of polarity and unsaturation of the lipid on the peptide-lipid interaction. The second specific aim is to determine the influence of the acyl chain length of the lipid on the peptide-lipid interaction. The self-assembly of phosphatidylcholine molecules is important for nanoemulsion formulations. Both theoretical and experimental studies have demonstrated that nanoemulsions have great potential for application as drug carriers for transdermal drug delivery. In this study, we also examine the binary systems at pH 3.8, where both lipids have the same headgroup, but different chain lengths, namely dimyristoylphosphatidylcholine/dipalmitoylphosphocholine (DMPC/DPPC) and dimyristoylglycerophosphorylglycerol/ dimyristoylglycerophosphorylglycerol (DMPG/DPPG). The third specific aim is to examine the influence of the metal ions on the peptide-lipid interactions. The hypothesis we make is that certain functional groups of Combi-2 interact with functional groups (phosphate, carbonyl and acyl chain of the lipid) of DPPC, palmitoyloleoylglycerophosphocholine (POPC), or cholesterol to form complexes. FTIR, fluorescence, TGA and DSC techniques revealed that combi-2 interacts strongly with polar and unsaturated lipids. FTIR, fluorescence, TGA and DSC techniques indicate that combi-2 interacts strongly with lipids of short acyl chain. Fluorescence data indicate that the intensity of combi-2 is quenched in the presence of metal ions. Interaction of combi-2 with unsaturated lipids in the presence of metal ions occurs through a conformational change, and the decrease in helix content depends on the nature of the metal ion. AFM images revealed that the interaction between combi-2 and POPC is stronger with calcium and lanthanum, as evidenced by the high values of roughness.^
"Investigating the structural impact of the antimicrobial peptide combi-2 in model membranes"
ETD Collection for Tennessee State University.