Optimization of the antimicrobial activity of magainin peptides by modification of charge
Optimization of the antimicrobial activity of magainin peptides by modification of charge
复制标题
DOI：
10.1016/s0014-5793(01)02648-5
复制
发表时间：
2001-07-20
期刊：
影响因子：
3.5
通讯作者：
Bienert, M
中科院分区：
文献类型：
--
作者：
Dathe, M;Nikolenko, H;Bienert, M
调查爪蟾抗菌肽II酰胺类似物的阳离子电荷范围在+3和+7之间显示，增强的肽电荷的阈值为+5和适当的疏水性的保护优化的抗微生物活性和选择性。高选择性是增强的抗微生物活性和降低的溶血活性的结果。电荷增加超过+5，保留其他结构基序，导致溶血活性的急剧增加和抗微生物选择性的损失。选择性可以通过减少疏水螺旋表面（H-hd）的疏水性来恢复，这是一个以前没有考虑过调节活性的结构参数。与脂质囊泡的染料释放实验表明，肽电荷调节膜活性的潜力是有限的：高度带负电荷的1-棕榈酰-2-油酰磷脂酰-DL-甘油双层，静电相互作用的加强有活性降低的效果。在中性的1-棕榈酰-2-油酰磷脂酰胆碱双层膜上，用H-hd测定了高活性。H-HD值高于一定阈值导致所有脂质系统的有效透化，甚至补偿了高度负电荷膜上电荷增加的活性降低效应。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
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.