新型阳离子抗菌肽的脂肪链修饰及抗菌活性

Fatty Chain Modification of New Cationic Antimicrobial Peptides and Study of Their Antimicrobial Activities

本研究以抗菌肽XAMP2(1)为模板,在其序列的N端(第2位氨基酸)、中间部位(第6位氨基酸)和C端(第10位氨基酸)分别连接棕榈酸、月桂酸和正辛酸脂肪链,设计了9条具有新型结构的抗菌肽(2~10),用固相合成法合成,以反相高效液相色谱法分离纯化,并用微量肉汤稀释法测定抗菌活性。改造后得到的抗菌肽5的抗菌活性较1有所提高,其抗大肠杆菌和铜绿假单胞菌的活性均为2μg/ml,比1增强2倍;其抗耐药鲍曼不动杆菌的活性为2μg/ml,比1增强4倍。同时还探讨了脂肪链长度和修饰位点对抗菌活性的影响。

Nine cationic antimicrobial peptides （2-10） were designed based on XAMP2 （1）by modifying fatty chains in different lysine positions. These antimicrobial peptides were synthesized by solid phase method and purified by RP-HPLC. Their antimicrobial activities were determined by broth microdilution method. The antimicrobial activity of peptides 5 was 2--4 times higher than that of 1, whose MICs against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumanii were 2 μg/ml. Meanwhile, the influence of fatty chain length and modification position on antimicrobial activity was also investigated.