Enhanced membrane permeabilization and antibacterial activity of a disulfide-dimerized magainin analogue
Enhanced membrane permeabilization and antibacterial activity of a disulfide-dimerized magainin analogue
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DOI：
10.1021/bi026328h
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发表时间：
2003-01-21
期刊：
影响因子：
2.9
通讯作者：
Avison, MB
中科院分区：
文献类型：
--
作者：
Dempsey, CE;Ueno, S;Avison, MB
比较了magainin-2酰胺的半胱氨酸取代类似物（magainin-F12W, N22C；这里用mag-N22C表示）和空气氧化制备的二硫链二聚体[(mag-N22C)(2)]从100 nm大单层囊泡（LUV）中释放羧基荧光素（CF）和杀死革兰氏阴性菌嗜麦芽寡养单胞菌和大肠杆菌的能力。与单体肽相比，二硫二聚肽表现出增强的渗透性和抗菌活性，特别是在极低的肽浓度下。低浓度二聚体在囊泡中增强的cf释放活性是由于(i)增强了与带负电荷的膜表面的结合，（ii）与单体相比，二聚体对渗透性的浓度依赖性较低。二聚体肽的独特性质表明蛙皮肤中抗菌肽的结构多样性，包括最近鉴定的由二硫化物连接的两亲螺旋肽组成的异源二聚体[Batista et al. (2001) FEBS Lett. 494, 85-89]。二硫二聚化成孔，带正电荷，两亲螺旋肽可能是一个有用的一般方法，以产生肽抗菌剂具有活性在非常低的浓度。
A cysteine substitution analogue of magainin-2 amide (magainin-F12W, N22C; denoted here as mag-N22C), and a disulfide-linked dimer prepared by air oxidation [(mag-N22C)(2)], were compared in their ability to release carboxyfluorescein (CF) from 100-nm large unilamellar vesicles (LUV) and to kill the Gram negative bacteria Stenotrophomonas maltophilia and Escherichia coli. The disulfide-dimerized peptide showed enhanced permeabilization and antimicrobial activity, when compared with the monomeric peptide, that was particularly marked at very low peptide concentrations. The enhanced CF-releasing activity of the dimer at low concentrations in vesicles results from (i) enhanced binding to negatively charged membrane surfaces and (ii) a low concentration dependence for permeabilization in the dimer compared to the monomer. The unique properties of the dimeric peptide suggest a role for structural diversity of antimicrobial peptides in frog skin, including the recent identification of a heterodimer composed of disulfide-linked amphipathic helical peptides [Batista et al. (2001) FEBS Lett. 494, 85-89]. Disulfide-dimerization of pore-forming, positively charged, amphipathic helical peptides may be a useful general approach to the generation of peptide antimicrobials having activity at very low concentrations.