title: Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae.
abstract: Circular dichroism and (1)H NMR were used to investigate the interactions of a series of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS) isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae. Previous CD studies with AMPs containing only three Tic-Oic dipeptide units do not exhibit helical characteristics upon interacting with small unilamellar vesicles (SUVs) consisting of LPS. Increasing the number of Tic-Oic dipeptide units to six resulted in five analogues with CD spectra that exhibited helical characteristics on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest that there are two possible helical conformations resulting from two different AMP-LPS binding mechanisms. Mechanism one involves a helical binding conformation where the AMP binds LPS very strongly and is not efficiently transported across the LPS bilayer resulting in the loss of inhibitory activity. Mechanism two involves a helical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity. Mechanism three involves a nonhelical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity.
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA.
authors.forename: Hanbo
authors.initials: H
authors.lastname: Chai
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Allen
authors.affiliation: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA ; Department of Chemistry and Physics, Georgia Regents University, College of Science and Mathematics, Augusta, GA 30904, USA.
authors.forename: Rickey P
authors.initials: RP
authors.lastname: Hicks