Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol

dc.contributor.advisorGammon, David Wen_ZA
dc.contributor.advisorSteenkamp, Danielen_ZA
dc.contributor.authorWatermeyer, Nicholas Den_ZA
dc.date.accessioned2015-04-02T14:18:19Z
dc.date.available2015-04-02T14:18:19Z
dc.date.issued2012en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractThis thesis describes the synthesis of several naphthoquinone- and carbazole-1,4-quinone-derived conjugates of a mycothiol-like scaffold designed to act as redox cycling subversive substrates of the enzyme, Mtr, or potentially inhibit other mycothiol-dependent or biosynthetic enzymes, in order to develop novel antitubercular lead compounds. The expression and purification of Mtr, as well as the attempts made towards the cloning and expression of active Mycobacterial glyoxalase I, in order to generate enzymes on which to assay the synthesised molecules, are also described. Linking of the quinone functionalities to the mycothiol-like scaffold, phenyl-1-thio-Dglucosamine, was envisaged to facilitate delivery of this class of redox active molecules to the active-site of the mycothiol enzymes. Successful completion of the synthesis of naphthoquinone conjugates of this scaffold was not achieved due to a persistent side reaction that took place during an N-tert-butoxycarbonyl deprotection step. However, this unexpected result led to the discovery of a new synthetic route to benzo[g]indoles and benzo[h]quinolines. This route differs from traditional quinoline and indole syntheses in that the aromatic C-N bond is generated by a condensation reaction between a quinone carbonyl and an aliphatic amine, rather than via the traditional condensation of an aromatic amine with a distal carbonyl group.en_ZA
dc.identifier.apacitationWatermeyer, N. D. (2012). <i>Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/12674en_ZA
dc.identifier.chicagocitationWatermeyer, Nicholas D. <i>"Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2012. http://hdl.handle.net/11427/12674en_ZA
dc.identifier.citationWatermeyer, N. 2012. Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Watermeyer, Nicholas D AB - This thesis describes the synthesis of several naphthoquinone- and carbazole-1,4-quinone-derived conjugates of a mycothiol-like scaffold designed to act as redox cycling subversive substrates of the enzyme, Mtr, or potentially inhibit other mycothiol-dependent or biosynthetic enzymes, in order to develop novel antitubercular lead compounds. The expression and purification of Mtr, as well as the attempts made towards the cloning and expression of active Mycobacterial glyoxalase I, in order to generate enzymes on which to assay the synthesised molecules, are also described. Linking of the quinone functionalities to the mycothiol-like scaffold, phenyl-1-thio-Dglucosamine, was envisaged to facilitate delivery of this class of redox active molecules to the active-site of the mycothiol enzymes. Successful completion of the synthesis of naphthoquinone conjugates of this scaffold was not achieved due to a persistent side reaction that took place during an N-tert-butoxycarbonyl deprotection step. However, this unexpected result led to the discovery of a new synthetic route to benzo[g]indoles and benzo[h]quinolines. This route differs from traditional quinoline and indole syntheses in that the aromatic C-N bond is generated by a condensation reaction between a quinone carbonyl and an aliphatic amine, rather than via the traditional condensation of an aromatic amine with a distal carbonyl group. DA - 2012 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol TI - Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol UR - http://hdl.handle.net/11427/12674 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/12674
dc.identifier.vancouvercitationWatermeyer ND. Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2012 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/12674en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleDesign and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiolen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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