Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49586
Title: QUANTITATIVE CHEMICAL PROTEOMICS INVESTIGATIONS OF TARGETS OF ANDROGRAPHOLIDE AND PROTEOLYSIS OF AUTOPHAGY
Authors: WANG JIGANG
Keywords: chemical biology, quantitative proteomics, drug targets, autophagy,proteolysis, metabolic labelling
Issue Date: 8-Oct-2013
Source: WANG JIGANG (2013-10-08). QUANTITATIVE CHEMICAL PROTEOMICS INVESTIGATIONS OF TARGETS OF ANDROGRAPHOLIDE AND PROTEOLYSIS OF AUTOPHAGY. ScholarBank@NUS Repository.
Abstract: The recently advanced quantitative proteomics approaches enabled the possibility of direct comparison of protein expressions for multiple samples in a high-throughput manner. Besides measuring the protein abundance changes, another important topic in proteomics is to provide direct information on protein activity and protein interaction, including protein-protein and protein-small molecule interactions. The emerging chemical proteomics offers a means to systematically analyse the protein activity and small molecule interaction other than protein abundance alone. In the first part of this thesis, we described a newly developed quantitative chemical proteomics approach which allows unbiased and specific drug target profiling. Using this method, a spectrum of specific targets of Andrographolide (Andro) was identified, revealing the mechanism of action of the drug and its potential novel application as a tumor metastasis inhibitor, which was validated through cell migration and invasion assays. Moreover, the target binding mechanism of Andro was unveiled with a combination of drug analogue synthesis, protein engineering and mass spectrometry-based approaches and the drug-binding sites of two protein targets, NF-?B p50 and actin, were determined. In the second part of this thesis, we present a novel method to determine the autophagic protein degradation level using chemical metabolic labeling. The sensitivity and accuracy of this new methodology was validated using different autophagy induction and inhibition approaches. The two projects, though independent of each other, have both demonstrated the critical role that quantitative chemical proteomics plays in today?s biomedical research.
URI: http://scholarbank.nus.edu.sg/handle/10635/49586
Appears in Collections:Ph.D Theses (Open)

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