Synthesis of Immunologically Relevant Glycoconjugates

Lee, Edward Jongyoon, Department of Chemistry, University of Virginia
McGarvey, Glenn, Department of Chemistry, University of Virginia
Macdonald, Timothy, Department of Chemistry, University of Virginia

Carbohydrates play a Variety of roles in many biological events. The aberrant expression of specific oligosaccharides on cell surfaces can indicate either a susceptibility to disease or an actual diseased state. These specific oligosaccharides are generally not Very immunogenic on their own, so carbohydrate - based Vaccines are generally composed of the specific disease - related oligosaccharide antigen connected to a strongly immunogenic biological entity. It is Very difficult to isolate pure oligosaccharides from biological sources in significant quantities, so through synthesis, pure oligosaccharides can be produced in significant quantities with the additional benefit of structural modifications that can allow for facile linking of the oligosaccharide to another component. In their native state, oligosaccharides are connected to either peptides or lipids through O - linkages, but these ether linkages can be susceptible to hydrolytic cleavage. One potential solution is to replace the O - linkage with a C - linkage that could also potentially enhance the immunogenicity of the oligosaccharide. The synthesis of the C - and O - glycopeptide analogues of the Thomson - Friedenreich (TF) antigen was completed. The C - and O - allyl analogues of the TF antigen were transformed into azido - alcohols and incorporated into a carbohydrate - Virus Vaccine construct. The C - and O - glycopeptide analogues of both the PK and oc - Gal antigens were also prepared, while significant progress was made towards the synthesis of the C - GM3 glycopeptide analogue.

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PHD (Doctor of Philosophy)
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