title: Correlations between membrane immersion depth, orientation, and salt-resistance of tryptophan-rich antimicrobial peptides.
abstract: 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.
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Yu
authors.forename: Bak-Sau
authors.initials: BS
authors.lastname: Yip
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Tu
authors.forename: Heng-Li
authors.initials: HL
authors.lastname: Chen
authors.forename: Hung-Lun
authors.initials: HL
authors.lastname: Chu
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Chih
authors.forename: Hsi-Tsung
authors.initials: HT
authors.lastname: Cheng
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Sue
authors.forename: Jya-Wei
authors.initials: JW
authors.lastname: Cheng
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011487:Protein Conformation; D012965:Sodium Chloride / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D008823:Micelles; D012965:Sodium Chloride; D014364:Tryptophan
keywords: Antimicrobial peptide; NMR; PRE; Salt-resistance; Tryptophan-rich