Effects of net charge and the number of positively charged residues on the biological activity of amphipathic α-helical cationic antimicrobial peptides
Effects of net charge and the number of positively charged residues on the biological activity of amphipathic α-helical cationic antimicrobial peptides
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DOI：
10.1002/bip.20911
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发表时间：
2008-01-01
期刊：
影响因子：
2.9
通讯作者：
Hodges, Robert S.
中科院分区：
文献类型：
--
作者：
Jiang, Ziqing;Vasil, Adriana I.;Hodges, Robert S.
在我们之前的研究中，我们利用26个残基的两亲性α螺旋抗菌肽L-V13K (Chen et al., Antimicrob Agents Chemother 2007, 51, 1398-1406)作为框架来研究肽疏水性对其抗菌作用机制的影响。在本研究中，我们探讨了L-V13K亲水/极性面上的净电荷和带正电残基的数量对其生物活性（抗菌和溶血）和生物物理特性（疏水性、两亲性、螺旋性和肽自缔合）的影响。 V13K 类似物在 pH 7 时的净电荷在 -5 和 +10 之间变化，带正电残基的数量在 1 到 10 之间变化。测定了对六种铜绿假单胞菌菌株以及其他革兰氏阴性和革兰氏阳性细菌的最小抑制浓度 (MIC)，以及不产生人红细胞溶血 (MHC) 的最大肽浓度。我们的结果表明，极性面上带正电荷的残基数量和净电荷对于抗菌活性和溶血活性都很重要。最引人注目的观察结果是 V13K i 极性面上增加一个正电荷时溶血活性的急剧转变。即，从+8到+9的变化导致溶血活性增加超过32倍(分别从250μg/ml到<7.8μg/ml)。 (c) 2007 年 Wiley 期刊公司。
In our previous study, we utilized a 26-residue amphipathic alpha-helical antimicrobial peptide L-V13K (Chen et al., Antimicrob Agents Chemother 2007, 51, 1398-1406) as the framework to study the effects of peptide hydrophobicity on the mechanism of its antimicrobial action. In this study, we explored the effects Of net charge and the number of positively charged residues on the hydrophilic/polar face of L-V13K on its biological activity (antimicrobial and hemolytic) and biophysical properties (hydrophobicity, amphipathicity, helicity, and peptide self-association). The net charge of V13K analogs at pH 7 varied between -5 and +10 and the number of positively charged residues varied from 1 to 10. The minimal inhibitory concentrations (MIC) against six strains of Pseudomonas aeruginosa as well as other gram-negative and gram-positive bacteria were determined along with the maximal peptide concentration that produces no hemolysis of human red blood cells (MHC). Our results show that the number of 1 positively charged residues on the polar face and net charge are both important for both antimicrobial activity and hemolytic activity. The most dramatic observation is the sharp transition of hemolytic activity on increasing one positive charge on the polar face of V13K i. e., the change from +8 to +9 resulted in greater than 32-fold increase in hemolytic activity (250 mu g/ml to < 7.8 mu g/ml, respectively). (c) 2007 Wiley Periodicals, Inc.