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dc.contributor.advisorItzstein, Mark von
dc.contributor.authorPascolutti, Mauro
dc.date.accessioned2018-01-23T02:29:26Z
dc.date.available2018-01-23T02:29:26Z
dc.date.issued2013
dc.identifier.doi10.25904/1912/2329
dc.identifier.urihttp://hdl.handle.net/10072/366410
dc.description.abstractInfluenza is a significant human disease, as evidenced by seasonal epidemics that exact a high toll in morbidity and mortality, and worldwide pandemics, for example the 2009 'swine-origin' influenza A pandemic. Two influenza virus-specific drugs, Relenza® and Tamiflu®, target the viral enzyme sialidase, and are effective against all wild type influenza virus strains. Resistance development to the more widely used drug, Tamiflu®, however, and new insights into the sialidase structure, have fuelled a drive to develop new sialidase inhibitors. The research described in this PhD thesis is focused on the development of novel carbohydrate-based inhibitors of influenza virus sialidase. This enzyme plays an important role in the process of infection by facilitating the release of new virus particles from the infected host cell. Inhibition of the viral sialidase leaves new virus particles clumped at the infected cell surface, thus reducing propagation of infection. Recent X-ray crystal structures of a sub-group of influenza A virus sialidases, which includes the important N1 sialidases, have revealed a previously unanticipated cavity adjacent to the enzyme active site, which is formed upon the opening of a flexible protein loop (the 150-loop). This offers the potential for the design of new sialidase inhibitors that target the open 150-loop conformation of the protein. Work published in the von Itzstein group has shown that suitable C-linked functionality introduced at the C3 position of the general sialidase inhibitor Neu5Ac2en, can extend into the 150-cavity and lock the flexible 150-loop in an open conformation. The research undertaken in this work, to further explore inhibition of influenza virus sialidase by targetting the 150-cavity, involved the synthesis of 3-O- and 3-N-substituted Neu5Ac2en derivatives.
dc.languageEnglish
dc.publisherGriffith University
dc.publisher.placeBrisbane
dc.rights.copyrightThe author owns the copyright in this thesis, unless stated otherwise.
dc.subject.keywordsInfluenza
dc.subject.keywordsInfluenza A pandemic
dc.subject.keywordsViral enzyme sialidase
dc.subject.keywordsRelenza®
dc.subject.keywordsTamiflu®
dc.subject.keywordsInfluenza virus sialidase
dc.titleThe Development of Carbohydrate-Based Probes of Influenza Virus Sialidase
dc.typeGriffith thesis
gro.facultyScience, Environment, Engineering and Technology
gro.rights.copyrightThe author owns the copyright in this thesis, unless stated otherwise.
gro.hasfulltextFull Text
dc.contributor.otheradvisorDyason, Jeff
dc.rights.accessRightsPublic
gro.identifier.gurtIDgu1368581532148
gro.source.ADTshelfnoADT0
gro.source.GURTshelfnoGURT
gro.thesis.degreelevelThesis (PhD Doctorate)
gro.thesis.degreeprogramDoctor of Philosophy (PhD)
gro.departmentInstitute for Glycomics
gro.griffith.authorPascolutti, Mauro


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