β-发卡抗菌肽的全新设计及其生物学活性

Design and biological activity of β-hairpin-like antimicrobial peptide

摘要:

通过缬氨酸和精氨酸的交替连接形成β-发卡结构的两条侧链，D-脯氨酸和甘氨酸形成β-转角单元以及侧链末端的两个半胱氨酸连接形成一个二硫键，来设计得到全新的由16残基构成的β-发卡抗菌肽VR。对设计得到的抗菌肽VR的生物学活性进行了检测，主要测定了新型β-发卡抗菌肽VR的最小杀菌浓度、对红细胞的溶血活性、杀菌动力学和盐敏感性。结果发现，VR和蜂毒素具有相似的杀菌活性，而溶血活性远低于蜂毒素，这表明VR比蜂毒素具有更高的细胞选择性。在NaCl的浓度低于100 mmol/L时，VR的杀菌活性没有受到影响；在NaCl的浓度为100 mmol/L时，VR具有50％的杀菌活性。综上可见，VR具有较优异的生物学活性，拥有成为抗生素替代物的发展潜力。

Abstract:

In the current study, we synthesized a 16-residue-long peptide VR with the aim of inspecting the feasibility to design β-hairpin-like antimicrobial peptide. The peptide was designed by alternating arrangement of arginine and valine and linking two stranded antiparallel β-sheet with a short loop segment (DPG) and a disulfide bridge. Antimicrobial and hemolytic activities were investigated. Melittin was chosen as a control peptide. We also tested bactericidal kinetics and salt sensitivity. Results show that VR had similar antibacterial activity compared with melittin. However, VR displayed much less hemolytic activity than melittin. These results suggest that VR had higher cell selectivity than melittin. The antibacterial activity of VR was not inhibited in the presence of 25 and 50 mmol/L NaCl. VR still possessed antibacterial activity in the presence of 100 mmol/L NaCl. Collectively, the de novo peptide VR displayed high antimicrobial activity, low hemolytic activity, and salt resistant, indicating that VR was a promising candidate for novel antimicrobial applications.