Hicks, Rickey P.Chai, Hanbo2014-08-282016-05-112014http://hdl.handle.net/10342/4526The wide application of antibiotics goes back over sixty years to the first use of penicillin in the mid-1940s. Antimicrobial agents have well-documented activity and have played a significant role in defending against various bacterial infections. However, antibiotic resistance has never ceased to undermine the efficacy of those compounds and has become a severe threat to patients with serious infections. It is imperative to discover and develop antibacterial agents with novel action mechanisms to lower the chance of drug resistance. A wide series of compounds called "antimicrobial peptides" (AMPs) have been either discovered in the nature or synthesized in laboratories around the world. The advent of AMPs has brought a new hope in the fight against the rise of antibiotic-resistant organisms.  Far-UV Circular Dichroism (CD) spectroscopy and 1H NMR have been used to investigate the interactions of a series of synthetic, unnatural amino acid-containing AMPs with Lipopolysaccharide (LPS) isolated from drug resistant Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae, along with various phospholipid compositions to better approximate the chemical makeup of the membranes of these two strains. The results showed that: (1) the binding interactions between the AMPs and the membranes are defined by the physicochemical properties of the peptide and the membrane model; (2) binding of these AMPs to the lipid A region (the innermost and phospholipid-like layer) of the LPS is stronger and dominant compared with the binding with the O-polysaccharide outer leaf moiety; (3) when different compositions of phospholipids were incorporated into the LPS to make a complete membrane model of the two strains, wavelength shifts in the CD spectra of the AMPs were observed that represents conformational changes of AMPs upon binding with the membrane model.  79 p.dissertations, academicChemistryAntimicrobial peptidesCircular dichroism spectroscopyGram-negative bacteriaLipopolysaccharidesMembrane modelsDrug resistance in microorganismsPeptide antibioticsPseudomonas aeruginosaKlebsiella pneumoniaeMaster's Thesis