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postgraduate thesis: Development of chemical reporters for glutarylation and HMGylation

TitleDevelopment of chemical reporters for glutarylation and HMGylation
Authors
Issue Date2014
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Xiong, Y. [熊鷹]. (2014). Development of chemical reporters for glutarylation and HMGylation. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5559005
AbstractProtein post-translational modifications (PTMs) are covalent chemical modifications that occur after protein translation. As such, PTMs have greatly expanded the diversity and complexity of proteomes. To understand this vital regulation system, study towards PTM has received intense attention in recent years. With the rapid advancements in mass-spectrometry technology, several new PTMs have been identified recently (e.g. lysine N-malonylation (2012), lysine N-succinylation (2012), and lysine N-glutarylation (2014)). To better understand those newly identified PTM substrates and discover potentially uncovered new PTMs, a chemical proteomics approach is proposed. To identify the substrates of a new PTM, namely, HMGylation, a chemical reporter HMG-AM-yne (2.1) is synthesized in 8 steps with 9.2% overall yield (Chapter 2). Meanwhile, to achieve a better understanding of the cell proteome-wide biodistribution of glutarylation substrates and its biological function, another reporter Glut-AM-yne (3.1) is synthesized in 6 steps with 9.3% overall yield (Chapter 3). To verify the existence of HMGylation and glutarylation on histones, standard peptides with HMGylation and glutarylation (H3K9 Glut and H3K9 HMG) are chemically synthesized by solid-phase peptide synthesis (SPPS) and the building block for peptide synthesis Fmoc-Glut-lys-tBu (4.1) and Fmoc-HMG-lys-all (4.21) are synthesized. To validate the labeling outcome of chemical reporter and map PTM sites, another two building blocks Fmoc-Glut-yne-lys-all (4.23) and Fmoc-HMG-yne-lys-all (4.25) are synthesized for H3K9 Glut-yne/HMG-yne standard peptide synthesis, as described in Chapter 4.
DegreeMaster of Philosophy
SubjectPost-translational modification
Proteomics
Dept/ProgramChemistry
Persistent Identifierhttp://hdl.handle.net/10722/216261

 

DC FieldValueLanguage
dc.contributor.authorXiong, Ying-
dc.contributor.author熊鷹-
dc.date.accessioned2015-09-08T23:11:34Z-
dc.date.available2015-09-08T23:11:34Z-
dc.date.issued2014-
dc.identifier.citationXiong, Y. [熊鷹]. (2014). Development of chemical reporters for glutarylation and HMGylation. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5559005-
dc.identifier.urihttp://hdl.handle.net/10722/216261-
dc.description.abstractProtein post-translational modifications (PTMs) are covalent chemical modifications that occur after protein translation. As such, PTMs have greatly expanded the diversity and complexity of proteomes. To understand this vital regulation system, study towards PTM has received intense attention in recent years. With the rapid advancements in mass-spectrometry technology, several new PTMs have been identified recently (e.g. lysine N-malonylation (2012), lysine N-succinylation (2012), and lysine N-glutarylation (2014)). To better understand those newly identified PTM substrates and discover potentially uncovered new PTMs, a chemical proteomics approach is proposed. To identify the substrates of a new PTM, namely, HMGylation, a chemical reporter HMG-AM-yne (2.1) is synthesized in 8 steps with 9.2% overall yield (Chapter 2). Meanwhile, to achieve a better understanding of the cell proteome-wide biodistribution of glutarylation substrates and its biological function, another reporter Glut-AM-yne (3.1) is synthesized in 6 steps with 9.3% overall yield (Chapter 3). To verify the existence of HMGylation and glutarylation on histones, standard peptides with HMGylation and glutarylation (H3K9 Glut and H3K9 HMG) are chemically synthesized by solid-phase peptide synthesis (SPPS) and the building block for peptide synthesis Fmoc-Glut-lys-tBu (4.1) and Fmoc-HMG-lys-all (4.21) are synthesized. To validate the labeling outcome of chemical reporter and map PTM sites, another two building blocks Fmoc-Glut-yne-lys-all (4.23) and Fmoc-HMG-yne-lys-all (4.25) are synthesized for H3K9 Glut-yne/HMG-yne standard peptide synthesis, as described in Chapter 4.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshPost-translational modification-
dc.subject.lcshProteomics-
dc.titleDevelopment of chemical reporters for glutarylation and HMGylation-
dc.typePG_Thesis-
dc.identifier.hkulb5559005-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineChemistry-
dc.description.naturepublished_or_final_version-

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