富含亮氨酸和精氨酸的抗菌肽设计

De novo Design of a Leu-Arg-rich Antimicrobial Peptide

通过构建亮氨酸疏水面和精氨酸亲水面来设计全新的抗菌肽,并评估利用这种螺旋轮投影模型设计出的抗菌肽的生物学活性。检测了设计得到的新型抗菌肽LGR16的最小抑菌浓度(MICs)、对于红细胞和哺乳动物细胞的细胞毒性以及杀菌动力学。结果表明,新型抗菌肽LGR16具有很强的抗菌活性,其对于革兰氏阴性菌和阳性菌的最小抑菌浓度分别为8和4μg.mL-1。LGR16杀菌速度快,在10min内能杀死细菌。在最小抑菌浓度该抗菌肽只表现出很弱的溶血活性和对哺乳动物细胞的细胞毒性。综上可见,抗菌肽能够通过在螺旋轮中聚集疏水性或者碱性氨基酸残基来设计,而且本研究得到的抗菌肽LGR16具有替代抗生素的潜质。

In this study,16-residue-long peptide（LGR16） was developed with the aim of inspecting the feasibility to design antimicrobial peptide by segregating hydrophobic residues in the nonpolar side and positively charged residues in the polar side based on the helical wheel projections.Antimicrobial activity,hemolytic activity,cytotoxicity against mammalian cells,and bactericidal kinetics were investigated to fully evaluate the biological function of the peptide.The results showed that the peptide LGR16 had strong antimicrobial activity,and it MICs against Gram-negative and Gram-positive bacteria were 8 and 4 μg·mL-1,respectively.LGR16 also exhibited rapid bactericidal action and had totally eradicated the bacteria within 10 min.LGR16 showed only weak hemolysis against chicken red blood cells and cytotoxicity aginst vero cells at its MICs,and the concentration that caused 50% hemolysis exceeded its MICs by over 8 times.Overall,antimicrobial peptides can be designed by assembling hydrophobic residues in the hydrophobic side and basic residues in the opposite side.The peptide LGR16 may be developed as a potent candidate for antimicrobial drugs.