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Investigation of the substrate specificity of recombinant Trypanosoma cruzi trans-sialidase

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JenniferHarrisonPhDThesis.pdf (25.88Mb)
Date
1999
Author
Harrison, Jennifer Amanda
Supervisor
Field, Rob
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Abstract
The protozoan blood-borne parasite Trypanosoma cruzi is the causative agent of Chagas' disease, an enervating and often fatal illness prevalent in South and Central America for which there is no effective treatment. T. cruzi has a cell-surface trans- sialidase which transfers sialic acid from mammalian oligosaccharides to the parasite. This action allows adhesion to and invasion of mammalian cells, subsequently allowing parasitic replication. This protein therefore is exploitable and represents a potential target for the development of chemotherapeutic agents. This thesis describes the purification of recombinant trans-sialidase and the development of a rapid, reliable spectrophotometric coupled assay to measure trans-sialidase activity. It also details the use of three mutually exclusive synthetic oligosaccharide libraries to map substrate recognition for the enzyme. Synthetic fragments of the natural branched oligosaccharide substrates have also been sialylated on a preparative scale, demonstrating the use of trans-sialidase in synthetic oligosaccharide chemistry.
Type
Thesis, PhD Doctor of Philosophy
Collections
  • Biology Theses
URI
http://hdl.handle.net/10023/14907

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