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dc.contributor.advisorDavid, Sunil
dc.contributor.authorShrestha, Anurupa
dc.date.accessioned2008-03-01T17:26:23Z
dc.date.available2008-03-01T17:26:23Z
dc.date.issued2007-12-19
dc.date.submitted2007
dc.identifier.otherhttp://dissertations.umi.com/ku:2349
dc.identifier.urihttp://hdl.handle.net/1808/1992
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 widevariety 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 antiendotoxin 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.format.extent124 pages
dc.language.isoEN
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectChemistry
dc.titleDesign, Syntheses, and Evaluation of Lipopolyamines as Anti-Endotoxin Agents
dc.typeThesis
dc.contributor.cmtememberDutta, Apurba
dc.contributor.cmtememberMitscher, Lester A.
dc.contributor.cmtememberHimes, Richard
dc.thesis.degreeDisciplineMedicinal Chemistry
dc.thesis.degreeLevelM.S.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
kusw.bibid6599345
dc.rights.accessrightsopenAccess


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