Optimization of the antimicrobial activity of magainin peptides by modification of charge

被引：337

作者：

Dathe, M ^{[1
]}

Nikolenko, H ^{[1
]}

Meyer, J ^{[1
]}

Beyermann, M ^{[1
]}

Bienert, M ^{[1
]}

机构：

[1] Res Inst Mol Pharmacol, D-13125 Berlin, Germany

来源：

FEBS LETTERS | 2001年 / 501卷 / 2-3期

关键词：

antibacterial peptide; magainin; peptide charge; hemolysis;

D O I：

10.1016/S0014-5793(01)02648-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Investigation of magainin II amide analogs with cationic charges ranging between +3 and +7 showed that enhancement of the peptide charge up to a threshold value of +5 and conservation of appropriate hydrophobic properties optimized the antimicrobial activity and selectivity. High selectivity was the result of both enhanced antimicrobial and reduced hemolytic activity. Charge increase beyond +5 with retention of other structural motifs led to a dramatic increase of hemolytic activity and loss of antimicrobial selectivity. Selectivity could be restored by reduction of the hydrophobicity of the hydrophobic helix surface (H-hd), a structural parameter not previously considered to modulate activity. Dye release experiments with lipid vesicles revealed that the potential of peptide charge to modulate membrane activity is limited: on highly negatively charged 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol bilayers, reinforcement of electrostatic interactions had an activity-reducing effect. On neutral 1-palmitoyl-2-oleoylphosphatidylcholine bilayers, the high activity was determined by H-hd. H-hd values above a certain threshold led to effective permeabilization of all lipid systems and even compensated for the activity-reducing effect of charge increase on highly negatively charged membranes. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：146 / 150

页数：5

共 29 条

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