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DC Field | Value | Language |
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dc.contributor.advisor | McGibbon, Graham A. | - |
dc.contributor.author | Zheng, Hongchao | - |
dc.date.accessioned | 2017-06-15T20:10:44Z | - |
dc.date.available | 2017-06-15T20:10:44Z | - |
dc.date.issued | 2007-08 | - |
dc.identifier.uri | http://hdl.handle.net/11375/21612 | - |
dc.description.abstract | <p> A variety of important cell functions rely on O-GlcNAcylation of proteins, a kind of post-translational glycosylation that modifies nuclear and cytoplasmic proteins on serine or threonine residues by the addition of the single sugar moiety β-N-acetylglucosamine (O-GlcNAc). Generally, two enzymes can catalyze the formation and cleavage of the O-GlcNAc O-glycosidic linkage. The O-GlcNAc transferase (OGT) catalyzes the transfer of N-acetylglucosamine from uridine diphosphate N-acetylglucosamine to the hydroxyl group of specific Thr and Ser residues. On the other hand, hydrolysis of the sugar moiety from proteins is achieved via the bi-functional nuclear cytoplasmic O-GlcNAcase and acetyltransferase (NCOAT). Since O-GlcNAcylation plays very important roles in many cell processes such as transcription, translation and protein-protein interaction, my research mainly focused on preparing compounds and developing methods to study the O-GlcNAcylation process and discover the structural information of OGT and NCOAT.</p> <p> In this thesis, the important enzyme substrates (YSDSPSTST for OGT and YSDSP(O-GlcNAc-Ser)TST for NCOAT) were prepared by solid phase synthesis and purified by preparative reverse phase HPLC. Their structure and sequence were confirmed by ESI-MS and tandem MS (MS/MS). The building block S-GlcNAc-Ac3-Ser-COOBn for preparing S-GlcNAcylated peptides was prepared by a multistep procedure. Two potent photoaffinity labeled probes for mapping the active site of sOGT were designed and synthesized, and their IC50 values for sOGT were measured by CapLC and a beta-elimination method. Also, many analytical methods were developed for studying the O-glcNAcylation, including discovering the O-Glycosylation site of peptides by MS/MS and beta-elimination methods, sequencing peptides by MS/MS, analyzing the protein digests by CapLC-MALDI MS and studying the ion mobility of peptides and glycopeptides using ion mobility spectrometry.</p> | en_US |
dc.language.iso | en_US | en_US |
dc.subject | compounds, methods, modification of proteins, cytoplasmic, glycosylation, hydrolysis, peptides | en_US |
dc.title | Compounds and Methods to Study O-GlcNAc Modification of Proteins | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Chemistry | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Zheng_Hongchao_2007Aug_Masters..pdf | 3.79 MB | Adobe PDF | View/Open |
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