人源抗菌肽LL-37衍生物GLL-37抗菌活性研究

Bactericidal activity of GLL-37,a novel derivative of the human antimicrobial peptide LL-37

目的:对人源抗菌肽LL-37的特定氨基酸残基进行替换,获得衍生抗菌肽GLL-37,以增强其抗蛋白酶解能力和抗菌活性。方法:肽LL-37和GLL-37均由化学合成。采用微量稀释法测定它们对6种革兰氏阴性和阳性菌的最低抑菌浓度,以及在不同NaCl浓度下,它们对大肠埃希菌ATCC 25922的最低抑菌浓度。将LL-37和GLL-37与弹性蛋白酶共孵育后,通过对共孵育产物进行蛋白聚丙烯凝胶电泳和抗菌活性测定,研究它们抗弹性蛋白酶水解的能力。结果:GLL-37较LL-37对弹性蛋白酶的水解作用更具抵抗力。在高浓度NaCl下,GLL-37也较LL-37具有更强的抗菌活性。结论:通过对LL-37氨基酸序列中特定氨基酸残基的替换,可增强其抗菌活性及抗弹性蛋白酶水解能力,获得的衍生肽GLL-37具有很高的研究开发价值。

Objective： To develop and investigate GLL-37,a substitution analogue of the human antimicrobial peptide LL-37 with anti-enzymatic degradation activity and improved efficacy. Methods： The bactericidal activities of LL-37 and newly developed GLL-37 against 6 Gramnegative and -positive bacteria were determined by Broth microdilution assays. The minimum inhibitory concentrations of LL-37 and GLL-37 against E. coli ATCC 25922 in different NaCl concentration medium were also detected. Both peptides were co-incubated with elastase,and then analyzed by PAGE electrophoresis and bactericidal activity determination. Results： GLL-37 showed a stronger elastase resistance ability than LL-37,and was significantly more effective than LL-37 under high-salt condition. Conclusion： The antimicrobial peptide GLL-37 derived form LL-37 has the potential as a new therapeutic agent for bacterial infections.