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dc.contributor.advisorTolbert, Thomas J
dc.contributor.authorHutchison, Kevin Michael
dc.date.accessioned2016-10-11T19:16:56Z
dc.date.available2016-10-11T19:16:56Z
dc.date.issued2015-12-31
dc.date.submitted2015
dc.identifier.otherhttp://dissertations.umi.com/ku:14300
dc.identifier.urihttp://hdl.handle.net/1808/21664
dc.description.abstractInterleukin 1 (IL-1) is an inflammatory cytokine that helps the immune system fight disease. The inflammatory action of IL-1 is regulated by the naturally occurring interleukin 1 receptor antagonist (IL-1ra). IL-1ra contains one N-linked glycosylation site and is expressed in humans in both glycosylated and non-glycosylated forms. The one current IL-1ra drug available (Kineret®) is expressed in Escherichia coli as a non-glycosylated form. Because of this, most studies of IL-1ra have been done with the non-glycosylated form and the effects of glycosylation have not been studied. This research attempts to study the effects of the glycosylation of IL-1ra with its binding to the interleukin 1 receptor type 1 (IL-1R1). Both IL-1R1 and IL-1ra were expressed in a glycosylation deficient strain of Pichia pastoris. In-vitro binding experiments between the two proteins were studied using both biolayer interferometry and size exclusion chromatography. Due to the long dissociation rate between IL-1ra and IL-1R1, biolayer interferometry was an unfeasible method. Size exclusion chromatography, however, proved to be a promising tool to study binding. Initial experiments with non-glycosylated IL-1ra showed a potential KD of 1.7 nM. Future studies need to be done using the glycosylated form of IL-1ra to determine any differences in binding between the glycosylated form and the non-glycosylated form.
dc.format.extent59 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsCopyright held by the author.
dc.subjectPharmaceutical sciences
dc.subject
dc.titleRole of Glycosylation of IL-1ra on its Binding to IL-1R1
dc.typeThesis
dc.contributor.cmtememberSiahaan, Teruna J
dc.contributor.cmtememberWang, Zhuo
dc.thesis.degreeDisciplinePharmaceutical Chemistry
dc.thesis.degreeLevelM.S.
dc.provenance04/05/2017: The ETD release form is attached to this record as a license file.
dc.rights.accessrightsopenAccess


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