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dc.contributor.authorWang, Xiaoyi
dc.date.accessioned2019-01-25T03:24:04Z
dc.date.available2019-01-25T03:24:04Z
dc.date.issued2018-09-29
dc.identifier.urihttp://hdl.handle.net/2123/19892
dc.description.abstractProteins are essential biomolecules that mediate a range of biological processes in humans. Many proteins contain post-translational modifications (PTMs) that are often vital to their biological activity and these modified proteins have recently attracted significant attention as promising therapeutics for the treatment of a range of diseases. Currently, most protein therapeutics are expressed as mixtures of isoforms containing different PTMs, which have a spectrum of biological activities. Understanding the importance and function of individual PTMs requires access to homogeneous protein isoforms, which can often only be achieved by chemical synthesis. Solid phase peptide synthesis (SPPS) combined with native chemical ligation (NCL)- desulfurization chemistry has led to the synthesis of a large number of protein targets with defined structure and function. In recent years, a new methodology called the diselenide-selenoester ligation (DSL) has proven to be a powerful complementary technology to NCL for the ligation of unprotected fragments to create native amide bonds. However, DSL technology, coupled with deselenization chemistry, is currently limited to ligation at alanine junctions due to a lack of availability of β-selenoamino acids other than selenocysteine (Sec, U). The overarching goal of the research described in this thesis therefore is to expand the utility of DSL through the generation of new β-selenoamino acid building blocks, and to validate their use in DSL through the construction of therapeutic protein targets. By enabling access to two extra ligation junctions (leucine and phenylalanine) for the expedient construction of complex post-translationally modified proteins by DSL-deselenization chemistry, this thesis has made important contributions to the area of protein science.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Scienceen_AU
dc.publisherSchool of Chemistryen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectpeptide ligationen_AU
dc.subject.otherincludes published articlesen_AU
dc.titleDevelopment and Application of Novel Methods for the Synthesis of Modified Proteinsen_AU
dc.typePhD Doctorateen_AU
dc.type.pubtypeDoctor of Philosophy Ph.D.en_AU
dc.description.disclaimerAccess is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.en_AU


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