Structural Characterization of de Novo Designed L5K5W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities

Molecules

Seo-Jin Kim¹  Jae-Seok Kim¹  Yoo-Sup Lee¹  Dae-Won Sim¹  Sung-Hee Lee¹  Young-Yil Bahk¹  Kwang-Ho Lee¹  Eun-Hee Kim¹  Sung-Jean Park¹  Bong-Jin Lee¹ 

[1] ¹Department of Biotechnology, Research Institute for Biomedical and Health Science, College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 380-701, Korea

关键词: amphipathic helical peptides;    antimicrobial peptides;    de novo design;    hemolytic activity;    L₅K₅W isomers;    structure-activity relationships;    tryptophan;   

DOI  :  10.3390/molecules18010859

来源: mdpi

【 摘 要 】

In an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L₅K₅W formula. Amino acid sequences were designed to be perfectly amphipathic when folded into a helical conformation by converging leucines onto one side and lysines onto the other side of the helical axis. The single tryptophans, whose positions were varied in the primary structures, were located commonly at the critical amphipathic interface in the helical wheel projection. Helical conformations and the tryptophanyl environments of the 11 L₅K₅W peptides were confirmed and characterized by circular dichroism, fluorescence and nuclear magnetic resonance spectroscopy. All of the isomers exhibited a potent, broad-spectrum of antibacterial activity with just a slight variance in individual potency, whereas their hemolytic activities against human erythrocytes were significantly diversified. Interestingly, helical dispositions and fluorescence blue shifts of the peptides in aqueous trifluoroethanol solutions, rather than in detergent micelles, showed a marked linear correlation with their hemolytic potency. These results demonstrate that our de novo design strategy for amphipathic helical model peptides is effective for developing novel antimicrobial peptides and their hemolytic activities can be estimated in correlation with structural parameters.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.