利用精氨酸和缬氨酸设计新型α-螺旋抗菌肽(英文)

Rational design of α-helical antimicrobial peptide with Val and Arg residues

【目的】抗菌肽是生命体的自身免疫系统的重要组成部分。其中两性的α-螺旋抗菌肽在抗菌肽家族中又占有重要的地位,发挥着重要的作用。为了得到具有更高抗菌活性同时具有很低细胞毒性的抗菌肽,根据α-螺旋二级结构衍生出来的螺旋轮模型,设计了一条在疏水一侧含有8个缬氨酸和亲水一侧含有5个精氨酸的新型16残基抗菌肽。【方法】测定了设计得到的新型抗菌肽的最小抑菌浓度、对于红细胞和哺乳动物肾细胞的细胞毒性以及杀菌动力学。【结果】抗菌活性检测表明,新型抗菌肽VGR16显示了强并快速的杀菌作用,其最小抑菌浓度在16-64μg/mL范围。溶血试验发现抗菌肽VGR16在检测的最大浓度256μg/mL处也未见溶血作用。细胞培养试验表明,抗菌肽VGR16对非洲猴肾细胞仅在很高浓度时具有很小的细胞毒性。【结论】综上可见,抗菌肽VGR16是具有很大抗菌潜力的抗生素替代物。

[Objective]The amphipathic α-helical peptide is an important class of antimicrobial peptides.In this study,a 16-residue-long peptide（VGR16） composed of 8 Val residues in the nonpolar face and 5 Arg residues in the polar face was designed based on the helical wheel projection to produce antimicrobial peptide with improved antibacterial activity accompanied by decreased toxicity.[Methods]Antimicrobial activity and toxicity against red blood cells and mammalian cells were investigated to evaluate the biological function of the peptide.In addition,bactericidal kinetics was tested.[Results]Antimicrobial assays revealed that the peptide VGR16 showed antimicrobial activity and their MICs against gram-negative and gram-positive bacteria ranged from 16 μg /ml to 64 μg /ml.VGR16 also exhibited rapid bactericidal action.It was surprisingly found that the peptide displayed no hemolytic activity even at a concentration of 256 μg /ml.Cell culture assays indicated that the peptide VGR16 had low cytotoxicity against mammalian cells.[Conclusion]The results showed that the peptide could be a likely candidate for future antimicrobial applications.