利用精氨酸和缬氨酸设计新型α-螺旋抗菌肽

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

摘要:

摘要：【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16－64

Abstract:

Abstract: [Objective] The amphipathic α-helical peptide is an important class of antimicrobial peptides. In this study, 16-residue-long peptide (VGR16) composed of 8 Val residues in the nonpolar face and 5 Arg residues in the polar face were 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 16μg/ml to 64μg/ml, respectively. 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 no cytotoxicity against mammalian cells for its MICs. [Conclusion] The results showed that the peptide could be a likely candidate for future antimicrobial applications.