AbstractLeishmaniasis is the second largest parasitic killer in the world (after malaria) responsible for an estimated 500,000 cases each year worldwide. Visceral leishmaniasis infections (i.e. internal organs) are more complicated to diagnose due to the lack of visible symptoms. Current tests of the disease look for antibodies against the parasite, but these antibodies are expressed long after the infection. It has been found the Leishmania parasite excretes a unique phosphoglycan repeat unit: By testing for this repeat unit, the diagnostic test will be looking for an active infection in the patient. It has been found that there are 4 monoclonal antibodies to detect this uniquely excreted phosphoglycan. This provides a basis for a test kit, the biomarker (i.e. the phosphoglycan repeats), and the way to detect the biomarker. For the construction of a dipstick style test or an ELISA format assay, a synthetic repeat unit phosphoglycan is needed to act as a positive control in a dipstick test or as a known comparison in a ELISA. The synthetic structure must also be anchored to a solid surface for testing. Biotin will be used as the anchor, it has shown many different uses in biotechnology and its very high affinity to the avidin proteins make it very useful. A 6-aminohexanol spacer arm will also be included. After many attempts to introduce the biotin spacer moiety to the repeat unit at the D-mannose 1-phosphate, it was decided to change the strategy and integrate the biotin-spacer moiety as a phosphate at the D-galactose unit. This meant performing chain elongation from the reducing end, with the first disaccharide unit being capped at the D-mannose anomeric position with a methyl group. Below are examples of the targeted biotinylated phosphoglycan structures to be prepared in this project.
|Date of Award||2011|
|Supervisor||Andrei Nikolaev (Supervisor)|
Chemical synthesis of Leishmania lipophosphoglycan structures conjugated to a biotin moiety
Edgar, C. W. (Author). 2011
Student thesis: Doctoral Thesis › Doctor of Philosophy