具有双活性序列的新型抗菌肽的设计及性质  

Design and Investigation of Novel Antimicrobial Peptides with Dual Active Sequences

作　　者：于岚岚[1] 毛烨炫[1] 白希希[1] 冉瑜[1] 李爱荣[2] 朱艳艳[1] 于斐[3] 屈凌波[1,4] 

机构地区：[1]郑州大学化学与分子工程学院,郑州450001 [2]郑州大学药学院,郑州450001 [3]郑州大学公共卫生学院,郑州450001 [4]河南工业大学化学化工学院,郑州450052

出　　处：《高等学校化学学报》2013年第5期1166-1173,共8页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21002093);教育部留学回国人员科研启动基金;中国博士后科学基金资助

摘　　要：设计合成了具有2个活性序列的线性和环状多肽及具有单个活性序列的短链多肽,研究了它们的杀菌活性、细胞毒性及溶血性.结果表明,线性肽和环状肽的杀菌活性高于短链肽.利用计算模拟的方法计算了多肽与细菌细胞膜中一种重要的成分磷脂酰甘油(DMPG)的结合能.结果表明,多肽-DMPG的结合能与多肽的杀菌活性具有较高的相关性,线性和环状多肽与DMPG的结合能大于短链肽.线性和环状多肽均含有2个活性序列,可提供多个荷正电氨基酸与荷负电的磷脂结合,结合能较大,杀菌活性较强.采用模拟生物膜对其中几条多肽的作用机理进行了初步研究.结果表明,该类多肽有可能使正常哺乳动物细胞的细胞膜产生孔洞;而对于细菌细胞膜,多肽并未在膜上产生明显孔洞,而是引起了细菌细胞膜的聚集.Short antimicrobial peptides Combi-1 and Combi-2 have been selected as bioactive sequences for new antimicrobial peptide design. Linear and cyclic peptides with two bioactive sequences were designed, synthesized, investigated and compared to short peptides with single bioactive sequence. The results show that the antibacterial activity of linear and cyclic peptides is higher than that of short peptides. The binding energy between peptides and an important component of bacterial membrane phosphatidylglyeerol （DMPG） was calculated by computer simulation. The results indicate that the binding energy between peptides and DMPG shows a high correlation to the antibacterial activity of peptides. The binding energy of linear or cyclic peptides with DMPG is also higher than that of short peptides. Linear and cyclic peptides with two bioactive sequences provide more positively charged amino acids, which bind to negatively charged phospholipid, leading to higher binding energy and stronger antibacterial activity. The computer simulation method provides theoretical evidence for antibacterial activity of antimierobial peptides to some extent. The linear peptides and one short peptide Combi-1 which are low production cost show high antibacterial activity, low eytotoxicity and hemolytic activity, indicating a research and application potential. The mechanism of some designed peptides interacting with biomembrane was briefly investigated via mimic membrane. Other than forming pores on the cytoplasmic membrane of normal mammalian cells, these peptides do not form pores on bacterial membrane, but induce membrane aggregation, which indicate that membrane is not the main target for these peptides to kill the bacteria.

关 键 词：抗菌肽 杀菌活性 多肽-磷脂相互作用 计算模拟 

分 类 号：O629[理学—有机化学]