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International Journal of Medicinal Chemistry
Volume 2014 (2014), Article ID 809283, 13 pages
http://dx.doi.org/10.1155/2014/809283
Research Article

Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae

1Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA
2Department of Chemistry and Physics, Georgia Regents University, College of Science and Mathematics, Augusta, GA 30904, USA

Received 27 August 2014; Revised 26 November 2014; Accepted 26 November 2014; Published 28 December 2014

Academic Editor: Armando Rossello

Copyright © 2014 Hanbo Chai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Circular dichroism and 1H 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.