title: Cell selectivity and interaction with model membranes of Val/Arg-rich peptides.
abstract: Antimicrobial peptides are major components of the innate self-defence system and a large number of peptides have been designed to study the mechanism of action. In the present study, a small combinatorial library was designed to study whether the biological activity of Val/Arg-rich peptides is associated with targeted cell membranes. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram-negative and Gram-positive bacteria, but weak haemolysis even at a concentration of 256 µM. CD spectra showed that the peptides formed α-helical-rich structure in the presence of negatively charged membranes. The tryptophan fluorescence and quenching experiments indicated that the peptides bound preferentially to negatively charged phospholipids over zwitterionic phospholipids, which corresponds well with the biological activity data. In the in vivo experiment, the peptide G6 decreased the bacterial counts in the mouse peritoneum and increased survival after 7 days. Overall, a high binding affinity with negatively charged phospholipids correlated closely with the cell selectivity of the peptides and some peptides in this study may be likely candidates for the development of antibacterial agents.
authors.affiliation: Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Ma
authors.forename: An-Shan
authors.initials: AS
authors.lastname: Shan
authors.forename: Na
authors.initials: N
authors.lastname: Dong
authors.forename: Yao
authors.initials: Y
authors.lastname: Gu
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Sun
authors.forename: Wan-Ning
authors.initials: WN
authors.lastname: Hu
authors.forename: Xing-Jun
authors.initials: XJ
authors.lastname: Feng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D014633:Valine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D010743:Phospholipids; D001120:Arginine; D014633:Valine