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dc.contributor.authorEmber, Brian
dc.date.accessioned2014-03-04T01:04:07Z
dc.date.available2014-03-04T01:04:07Z
dc.date.issued2006-05
dc.identifier.otherember_brian_200605_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/ember_brian_200605_phd
dc.identifier.urihttp://hdl.handle.net/10724/23107
dc.description.abstractRational drug design remains one of the best methods in the development of newpharmaceutical compounds. The cyclic research pattern of testing and derivatizing thesecompounds requires the ability to rigorously study the biomolecular kinetics of both thenatural substrate – protein interaction as well as that of the derivatives with the nativeprotein. Regardless of whether the desired outcome is inhibition, signal transduction orenhanced avidity, greater knowledge of the system will facilitate better medicinalcompounds in a shorter period of time.Over the past few decades, the importance of oligosaccharides as importantbiological ligands in a variety of immune associated and disease related pathways havemade them attractive targets for synthetic medicinal chemists. Along with the ability toalter selectivities via changes in linking patterns and derivitization, utilization ofmultivalency, found throughout nature with sugar interactions, greatly enhances affinitywithout the need of a tight-binding ligand. The increased affinities of multivalentsaccharides have been exploited in the synthetic design of inhibitors for bacterial toxinsas well as blocking the binding for viruses to cells.This dissertation combines the efforts of studying small molecule – proteininteractions with the importance of oligosaccharide chemistry as biological markers insynthesis as well as assay development. Monovalent and polyvalent synthetic substratescontaining terminal sialic acid were investigated as to their effectiveness as a substratetoward three modular sialidases and one without a carbohydrate binding domain. Theresulting novel mechanism unraveled resulted in the design of novel selective inhibitorsfor bacterial sialidases. Furthermore, new studies of human proteins believed to take partin immune recognition were assayed with surface plasmon resonance technology utilizingglycopeptide part structures synthesized in the Boons’ laboratory. The kinetic studies ofthese part structures led to the understanding that one of the proteins studied is highlyselective toward the recognition of DAP-type peptidoglycan.Index Words: Carbohydrate, Multivalency, Sialidase, Neuraminidase, Kinetics,Peptidoglycan, Surface Plasmon Resonance, Peptidoglycan Recognition Proteins
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectCarbohydrate
dc.subjectMultivalency
dc.subjectSialidase
dc.subjectNeuraminidase
dc.subjectKinetics
dc.subjectPeptidoglycan
dc.subjectSurface Plasmon Resonance
dc.subjectPeptidoglycan Recognition Proteins
dc.titleAssay development and kinetic studies of protein-small molecule interactions
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentChemistry
dc.description.majorChemistry
dc.description.advisorGeert-Jan Boons
dc.description.committeeGeert-Jan Boons
dc.description.committeeRobert Phillips
dc.description.committeeRobert Woods


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