Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides  

作　　者：Ming Kai Wei Zhang Huan Xie Liwei Liu Sujie Huang Xiao Li Zhengzheng Zhang Yuyang Liu Bangzhi Zhang Jingjing Song Rui Wang 

机构地区：[1]School of Life Sciences, Lanzhou University, Lanzhou 730000, China [2]Laboratory of Preclinical Study for New Drugs of Cansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China

出　　处：《Chinese Chemical Letters》2018年第7期1163-1166,共4页中国化学快报（英文版）

基　　金：the National Natural Science Foundation of China(Nos. 81773566, 21602092, 81473095);the Fundamental Research Funds for the Central Universities(Nos. lzujbky-2017-134, lzujbky-2017-120, lzujbky-2016-21)

摘　　要：Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker,and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtained via assessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker,and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtained via assessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.

关 键 词：Linker amino acid Flexibility Heteromeric antimicrobial peptides Potency and selectivity 

分 类 号：O629.72[理学—有机化学]