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DC Field | Value | Language |
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dc.contributor.author | Malkowski, Sarah Nicole | - |
dc.date.accessioned | 2014-06-11T16:52:22Z | - |
dc.date.available | 2014-06-11T16:52:22Z | - |
dc.date.issued | 2014-05 | - |
dc.identifier.uri | http://hdl.handle.net/10267/21141 | - |
dc.description | Sarah Malkowski granted permission for the digitization of his paper. It was submitted by CD. | en_US |
dc.description.abstract | Currently, there are limited therapies to effectively treat Gram-negative bacterial infections. Compared to Gram-positive bacteria, Gram-negative bacteria have an additional peptidoglycan outer membrane composed of lipopolysaccharide (LPS). Lipid A, an integral component of LPS, is essential for bacterial virulence and pathogenicity. LpxC catalyzes the first committed step in the biosynthetic pathway of lipid A, making it an attractive target for inhibition. This work focuses on probing the active site of LpxC through the synthesis of natural substrate analogues in order to develop a novel broadspectrum inhibitor. The natural substrate has three key features to bind in the active site: a nucleoside containing uracil to bind in the polar region, a diphosphate to coordinate to the zinc ion, and a substituted glucosamine with a long hydrocarbon chain to interact with the residues in the hydrophobic passage. With this in mind, the analogues contain uracil bound to a ribose or acyclic sugar that is connected to an amino acid-containing hydroxamic acid through an ether linkage or triazole linkage. Four analogues, two with the ribose and two with the acyclic sugar, were synthesized to their carboxylic acid intermediates, and a method has been detennined to convert the carboxylic acid intermediate to the hydroxamic acid compound. An analogue containing uridine coupled to an amino acid-containing hydroxamic acid via a triazole linker was successfully synthesized in seven steps. | en_US |
dc.description.sponsorship | This Honors paper was read and approved by Larryn W., Peterson, Mauricio Cafiero, and Laura Luque de Johnson. | en_US |
dc.publisher | Memphis, Tenn. : Rhodes College | en_US |
dc.rights | Rhodes College owns the rights to the archival digital objects in this collection. Objects are made available for educational use only and may not be used for any non-educational or commercial purpose. Approved educational uses include private research and scholarship, teaching, and student projects. For additional information please contact archives@rhodes.edu. Fees may apply. | - |
dc.subject | Text | - |
dc.subject | Chemistry, Department of | en_US |
dc.subject | Student research | en_US |
dc.subject | Honors papers | en_US |
dc.title | Probing the Active Site of LpxC in Gram-Negative Bacteria: Design and Synthesis of Acyclic Natural Substrate Analogues | en_US |
dc.type | Thesis | en_US |
Appears in Collections: | Honors Papers |
Files in This Item:
File | Description | Size | Format | |
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malkowski_honors_complete.pdf | 12.92 MB | Adobe PDF | View/Open |
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