Peptide-induced membrane leakage by lysine derivatives of gramicidin A in liposomes, planar bilayers, and erythrocytes

• Published in: Biochimica et biophysica acta Vol. 1828; no. 11; pp. 2428 - 2435
• Main Authors: Sorochkina, Alexandra I., Kovalchuk, Sergei I., Omarova, Elena O., Sobko, Alexander A., Kotova, Еlena А., Antonenko, Yuri N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2013
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Channel; Erythrocyte; Erythrocytes - drug effects; Gramicidin - chemistry; Gramicidin - pharmacology; Gramicidin A; Leakage; Lipid Bilayers; Liposome; Lysine - chemistry; Lysine - pharmacology; Molecular Sequence Data; Peptide; Peptides - pharmacology; Spectrometry, Fluorescence; Leakage; SRB; BLM; CF; EggPC; Gramicidin A; Channel; Liposome; DPhPC; Erythrocyte; PEG; FCS; Rh–PE; gA; AlPcS4; Peptide; diphytanoylphosphatidylcholine; egg yolk phosphatidylcholine; carboxyfluorescein; tetrasulfonated aluminum phthalocyanine; fluorescence correlation spectroscopy; polyethylene glycol; AlPcS; sulforhodamine; bilayer lipid membrane; rhodamine–phosphatidylethanolamine
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2013.06.018

Introducing a charged group near the N-terminus of gramicidin A (gA) is supposed to suppress its ability to form ion channels by restricting its head-to-head dimerization. The present study dealt with the activity of [Lys1]gA, [Lys3]gA, [Glu1]gA, [Glu3]gA, [Lys2]gA, and [Lys5]gA in model membrane systems (planar lipid bilayers and liposomes) and erythrocytes. In contrast to the Glu-substituted peptides, the lysine derivatives of gA caused non-specific liposomal leakage monitored by fluorescence dequenching of lipid vesicles loaded with carboxyfluorescein or other fluorescent dyes. Measurements of electrical current through a planar lipid membrane revealed formation of giant pores by Lys-substituted analogs, which depended on the presence of solvent in the bilayer lipid membrane. The efficacy of unselective pore formation in liposomes depended on the position of the lysine residue in the amino acid sequence, increasing in the row: [Lys2]gA<[Lys5]gA<[Lys1]gA<[Lys3]gA. The similar series of potency was exhibited by the Lys-substituted gA analogs in facilitating erythrocyte hemolysis, whereas the Glu-substituted analogs showed negligible hemolytic activity. Oligomerization of the Lys-substituted peptides is suggested to be involved in the process of nonselective pore formation.
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•Monosubstituted lysine derivatives of gramicidin A caused liposomal leakage.•Leakage depended on the position of the lysine residue in amino acid sequence.•Lys-substituted gramicidin analogs induced erythrocyte hemolysis.•Aggregation of Lys-substituted peptides could be involved in the leakage induction.