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dc.contributor.authorShrestha, Anurupa
dc.descriptionThesis (M.S.)--University of Kansas, Medicinal Chemistry, 2007.en_US
dc.description.abstractEndotoxins, or Lipopolysaccharides (LPS) present on the surface of Gram negative bacteria play a key role in the pathogenesis of septic shock, a common clinical problem and a leading cause of mortality in critically ill patients, for which no specific modalities are available at the present time. The toxic moiety of LPS is a glycolipid called Lipid A, which is composed of a bis-phosphorylated diglucosamine backbone bearing up to seven acyl chains in ester and amide linkages. Lipid A is structurally highly conserved in Gram negative bacteria, and is therefore an attractive target for developing anti-endotoxin molecules designed to sequester, and thereby neutralize, the deleterious effects of endotoxin.

The anionic and amphipathic nature of Lipid A enables the interaction of a wide variety of cationic amphiphiles with the toxin. A systematic evaluation of several structural classes of cationic amiphiphiles both peptidic and non-peptidic small molecules, in the broader context of recent efforts aimed at developing novel anti-endotoxin strategies. The derivation for the pharmacophore for LPS recognition has led to the identification of novel, nontoxic, structurally simple molecules, the lipopolyamines. The lipopolyamines bind and neutralize LPS in in vitro experiments as well as in animal models of endotoxicity, and thus present novel and exciting leads for rational, structure-based development of LPS sequestering agents of potential clinical value.
dc.publisherUniversity of Kansasen_US
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.en_US
dc.subjectHealth and environmental sciencesen_US
dc.subjectPure sciencesen_US
dc.subjectBiological sciencesen_US
dc.titleDesign, syntheses, and evaluation of lipopolyamines as anti-endotoxin agentsen_US
dc.thesis.degreeDisciplineMedicinal Chemistry

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