Correlations between membrane immersion depth, orientation, and salt-resistance of tryptophan-rich antimicrobial peptides

被引:19
|
作者
Yu, Hui-Yuan [1 ,2 ]
Yip, Bak-Sau [1 ,2 ,3 ]
Tu, Chih-Hsiang [1 ,2 ]
Chen, Heng-Li [1 ,2 ]
Chu, Hung-Lun [1 ,2 ]
Chih, Ya-Han [1 ,2 ]
Cheng, Hsi-Tsung [1 ,2 ]
Sue, Shih-Che [4 ,5 ]
Cheng, Jya-Wei [1 ,2 ]
机构
[1] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 300, Taiwan
[2] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 300, Taiwan
[3] Natl Taiwan Univ Hosp, Hsinchu Branch, Dept Neurol, Hsinchu 300, Taiwan
[4] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Hsinchu 300, Taiwan
[5] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 300, Taiwan
来源
关键词
Antimicrobial peptide; Tryptophan-rich; Salt-resistance; NMR; PRE; MICELLE-BOUND PEPTIDES; PSEUDOMONAS-AERUGINOSA; RATIONAL DESIGN; CYSTIC-FIBROSIS; HYDROPHOBICITY; ANTIBACTERIAL; MECHANISM; CHARGE; NMR; PERMEABILIZATION;
D O I
10.1016/j.bbamem.2013.07.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The efficacies of many antimicrobial peptides are greatly reduced in the presence of high salt concentrations therefore limiting their development as pharmaceutical compounds. PEM-2-W5K/A9W, a short Trp-rich antimicrobial peptide developed based on the structural studies of PEM-2, has been shown to be highly active against various bacterial strains with less hemolytic activity. Here, correlations between membrane immersion depth, orientation, and salt-resistance of PEM-2 and PEM-2-W5K/A9W have been investigated via solution structure and paramagnetic resonance enhancement studies. The antimicrobial activities of PEM-2-W5K/A9W and PEM-2 against various bacterial and fungal strains including multidrug-resistant and clinical isolates under high salt conditions were tested. The activities of the salt-sensitive peptide PEM-2 were reduced and diminished at high salt concentrations, whereas the activities of PEM-2-W5K/A9W were less affected. The results indicated that the strong salt-resistance of PEM-2-W5K/A9W may arise from the peptide positioning itself deeply into microbial cell membranes and thus able to disrupt the membranes more efficiently. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:2720 / 2728
页数:9
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