The development of S-glycosylcysteine derivatives for use in glycan-binding assays

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dc.contributor.advisorGammon, David Wen_ZA
dc.contributor.authorWilliams, Matthewen_ZA
dc.date.accessioned2017-10-12T14:07:11Z
dc.date.available2017-10-12T14:07:11Z
dc.date.issued2017en_ZA
dc.description.abstractThis dissertation concerns the development of a synthetic route towards novel cysteine-based glycan-binding probes, for incorporation into glycoarrays and or similar applications used in assays of glycan-recognition phenomena. The need to systematically characterize the glycome and decipher the range of glycosylation patterns found in living cells, has prompted the development of molecular tools such as glycoarrays and related systems for immobilizing defined carbohydrate structures. The preparation of these probes requires access to building blocks where the core structure has defined glycans together with appropriate linkers, and the amino acid cysteine is explored here as one such structure. In particular, this dissertation describes the synthesis of a S-glucosylcysteine derivative SGC, or methyl N-(6-aminohexanoyl)-S-(β-D-glucopyranosyl)-L-cysteinate trifluoroacetate 67, as well as its 2-acetamido analogue SAGC, or methyl N-(6-aminohexanoyl)-S-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-cysteinate trifluoroacetate 74. The first approach involved initial preparation of N-(4-azidobutanoyl)-L-cysteine 12 and attempted reaction of this with 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 3 to form the initial target of this dissertation, bis-glucoside 13. This was not successful, but repetition of the reported reaction involving the use of N-acetyl-L-cysteine 4 provided a modest yield of partially purified bis-glucosyl cysteine (BGC, 1). A mechanism for this one-pot, sequential bis-glucosylation is proposed. The limitations of the one-pot procedure led to investigation of alternative methods for the step-wise introduction of sugar units to the cysteine core. For this purpose the cysteine derivative, methyl N-(6-((tert-butoxycarbonyl)amino)hexanoyl)-L-cysteinate 40, was prepared and reacted with 3 to obtain a fully protected precursor of the target SGC. However, inefficiencies in this procedure led to investigation of an alternative strategy for preparation of SGC.en_ZA
dc.identifier.apacitationWilliams, M. (2017). <i>The development of S-glycosylcysteine derivatives for use in glycan-binding assays</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/25655en_ZA
dc.identifier.chicagocitationWilliams, Matthew. <i>"The development of S-glycosylcysteine derivatives for use in glycan-binding assays."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2017. http://hdl.handle.net/11427/25655en_ZA
dc.identifier.citationWilliams, M. 2017. The development of S-glycosylcysteine derivatives for use in glycan-binding assays. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Williams, Matthew AB - This dissertation concerns the development of a synthetic route towards novel cysteine-based glycan-binding probes, for incorporation into glycoarrays and or similar applications used in assays of glycan-recognition phenomena. The need to systematically characterize the glycome and decipher the range of glycosylation patterns found in living cells, has prompted the development of molecular tools such as glycoarrays and related systems for immobilizing defined carbohydrate structures. The preparation of these probes requires access to building blocks where the core structure has defined glycans together with appropriate linkers, and the amino acid cysteine is explored here as one such structure. In particular, this dissertation describes the synthesis of a S-glucosylcysteine derivative SGC, or methyl N-(6-aminohexanoyl)-S-(β-D-glucopyranosyl)-L-cysteinate trifluoroacetate 67, as well as its 2-acetamido analogue SAGC, or methyl N-(6-aminohexanoyl)-S-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-cysteinate trifluoroacetate 74. The first approach involved initial preparation of N-(4-azidobutanoyl)-L-cysteine 12 and attempted reaction of this with 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 3 to form the initial target of this dissertation, bis-glucoside 13. This was not successful, but repetition of the reported reaction involving the use of N-acetyl-L-cysteine 4 provided a modest yield of partially purified bis-glucosyl cysteine (BGC, 1). A mechanism for this one-pot, sequential bis-glucosylation is proposed. The limitations of the one-pot procedure led to investigation of alternative methods for the step-wise introduction of sugar units to the cysteine core. For this purpose the cysteine derivative, methyl N-(6-((tert-butoxycarbonyl)amino)hexanoyl)-L-cysteinate 40, was prepared and reacted with 3 to obtain a fully protected precursor of the target SGC. However, inefficiencies in this procedure led to investigation of an alternative strategy for preparation of SGC. DA - 2017 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - The development of S-glycosylcysteine derivatives for use in glycan-binding assays TI - The development of S-glycosylcysteine derivatives for use in glycan-binding assays UR - http://hdl.handle.net/11427/25655 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/25655
dc.identifier.vancouvercitationWilliams M. The development of S-glycosylcysteine derivatives for use in glycan-binding assays. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2017 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/25655en_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.titleThe development of S-glycosylcysteine derivatives for use in glycan-binding assaysen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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