一组含卤素阳离子抗菌肽的制备、抗菌活性和溶血毒性测定  

Synthesis as Well as Determination of the Antimicrobial Activities and Haemolytic Activities of Halogen-contained Cationic Antimicrobial Peptides

作　　者：唐汉卿 李盈淳 东圆珍[2] 王岩[2] 冯军[2] 

机构地区：[1]浙江工业大学、长三角绿色制药协同创新中心,浙江杭州310014 [2]中国医药工业研究总院上海医药工业研究院、创新药物与制药工艺国家重点实验室,上海201203 [3]正大天晴药业集团股份有限公司,江苏南京210038

出　　处：《中国医药工业杂志》2016年第12期1513-1518,共6页Chinese Journal of Pharmaceuticals

基　　金：国家“重大新药创制”科技重大专项(2014ZX09507009-024)

摘　　要：本研究以抗菌肽F-K-K-L-L-K-K-L-R-K-F-NH2（1）为模板,通过卤素苯丙氨酸的替换和硫醚键环化的方式,设计了10条具有新型结构的阳离子抗菌肽（2~11）,用固相合成法合成直链肽,碱性条件下环化生成环肽。采用反相高效液相色谱法分离纯化,以微量肉汤稀释法测定抗菌肽的最低抑菌浓度（MIC）,使用脱纤维羊血测定其溶血毒性。结果显示,改造后得到的抗菌肽10的抗菌活性比1有显著提高,对大肠埃希菌的MIC为1μg/ml,活性是1的4倍;对耐药鲍曼不动杆菌的MIC为4μg/ml,活性是1的8倍。Ten pieces of novel cationic antimicrobial peptides （2-11） were designed based on the antimicrobial peptide F-K-K-L-L-K-K-L-R-K-F-NH2 （1） by replacing phenylalanine with halogen-contained phenylalanine and cyclizing with sulfide bond. These antimicrobial peptides were synthesized with solid phase method, cyclized under alkaline conditions and purified by RP-HPLC. Their antimicrobial activities were determined by the broth microlilution procedure, and haemolytic activities were determined by using sterile defidrinated sheep blood. The antimicrobial activity of 10 was higher than that of 1, whose MIC against Escherichia coli was 1μg/ml, and the antimicrobial activity was four times as much as that of 1. Its MIC against Acinetobacter baumanii was 4 μg/ml, and the antimicrobial activity was about eight times the activity of 1.

关 键 词：固相多肽合成 环化 抗菌活性 溶血毒性 

分 类 号：R978.16[医药卫生—药品]