Design and Synthesis of Amphiphilic Basic Peptides with Antibacterial Activity and Their Interaction with Model Membrane

Abstract

Twelve peptides having 4 to 6 basic amino acid residues in the hydrophobic amino acid sequence were designed and synthesized by the solution method to find peptides with potential activity against Gram-positive and -negative bacteria. CD study of the peptides demonstrated that they formed α-helical structures in the presence of phospholipid liposomes consequently to have amphiphilic property along the axis of helix. The peptides also induced the leakage of the dye carboxyfluorescein from phospholipid vesicles, indicating that the peptides possess the ability to perturb the membrane structure. These peptides showed antibacterial activity against Gram-positive bacteria, and some of them were also active against Gram-negative bacteria. Relationships between the structure and antibacterial activity of the synthetic peptides were discussed.

Zinc-Induced Conformational Transitions of Acidic Peptides: Characterization by Circular Dichroism and Electrospray Mass Spectrometry

“…Several properties of the a-helix have been utilized to force short peptides to adopt this conformation. Physical factors, such as the action of surfactants [25] or of liposomes, [26] help the formation of the structures of 13-and 12-residue peptides, respectively. Helixdipole stabilization has been obtained by the modification of the charged groups near the termini of the 13-residue C-peptide of ribonuclease A.…”

Interactions of basic amphiphilic peptides with dimyristoylphosphatidylcholine small unilamellar vesicles: Optical, NMR, and electron microscopy studies and conformational calculations

“…Up to now, several experimental approaches have been employed for the study of the interactions between polypeptides and membranes or membrane models, and many of them use synthetic polypeptides able to mimic the natural compounds and their biologically relevant activity when interacting with a membrane (Anantharamaiah et al, 1985;Schlegel & Wade, 1985; Ho & De Grado, 1987;Lee et al, 1987;Mihara et al, 1987;Houbre et al, 1988;Ono et al, 1988Ono et al, , 1990Suenaga etal., 1988;Bruner, 1989;Kono etal., 1990;Takahashi, 1990; Clagueetal., 1991; Kato etal., 1991;Lee etal., 1992; Maget-Dana & Trudelle, 1991;Mac Lean et al, 1991; Merulka & Stellwagen, 1991; Mosior & McLaughlin, 1992;Yeagle et al, 1991).…”

Interaction of bundled Ser-rich amphiphilic peptides with phospholipid membranes

“…The membraneperturbing activity of a short model peptide, Ac-(LeuAla-Arg-Leu) 3 -NHCH 3 , was weaker compared with that of the bundled peptides. Nevertheless, the short peptide showed a strong antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis [28]. It can be said that activities observed for a lipid membrane do not always reflect those of the cell membrane.…”

“…Antibacterial activity of the peptides was examined for reference by the standard agar dilution method as described by Mihara et al [28]. None of the bundled peptides showed growth inhibitory activity at peptide concentrations of less than 100 mg/ml against Grampositive and -negative bacteria, although they had a strong membrane-perturbing activity for DPPC and DPPC/DPPG (3:1) vesicles at 50°C.…”