Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated fromPseudomonas aeruginosaandKlebsiella pneumoniae

[摘要] Circular dichroism and1H NMR were used to investigate the interactions of aseries of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS) isolated fromPseudomonas aeruginosaandKlebsiella pneumoniae. Previous CD studies with AMPscontaining only three Tic-Oic dipeptide units do not exhibit helical characteristics uponinteracting with small unilamellar vesicles (SUVs) consisting of LPS. Increasing the number ofTic-Oic dipeptide units to six resulted in five analogues with CD spectra that exhibited helicalcharacteristics on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest thatthere are two possible helical conformations resulting from two different AMP-LPS bindingmechanisms. Mechanism one involves a helical binding conformation where the AMP bindsLPS very strongly and is not efficiently transported across the LPS bilayer resulting in the loss ofinhibitory activity. Mechanism two involves a helical binding conformation where the AMPbinds LPS very loosely and is efficiently transported across the LPS bilayer resulting in anincrease in inhibitory activity. Mechanism three involves a nonhelical binding conformationwhere the AMP binds LPS very loosely and is efficiently transported across the LPS bilayerresulting in an increase in inhibitory activity.

[学科分类] 药学