Stereoselective Synthesis of Plant and Animal-Derived O-linked Glycopeptides

Abstract

This thesis describes efforts towards the stereoselective synthesis of homogeneous plant and animal-derived O-linked glycopeptides for the purposes of interrogating structure-function relationships. The first section of this thesis (chapter 2) details the synthesis of novel CLE and CEP glycopeptide plant hormones which bear the plant-specific β1,2-triarabinosylated hydroxyproline motif. The hormones which were synthesised have been linked to the root growth programme in legumes (Medicago truncatula and Soybean), but have not previously been structurally characterised. One of these glycopeptides, MtCLE13, was biologically evaluated and was shown to possess nodulation inhibiting properties only when triarabinosylated at the key hydroxyproline residue, thus confirming the critical functional role of the carbohydrate moiety. The second section of this thesis (chapters 3-5) describes efforts towards the stereoselective synthesis of human cell membrane-derived MUC1 glycopeptides containing α-sialylated tumour-associated carbohydrate antigens (sialyl Tn, 2,6-sialyl T, 2,3-sialyl T and glycophorin antigens). The work described in these chapters culminated in the development of a divergent and highly stereoselective synthetic route to all of the key glycosylamino acids required for the construction of a library of homogeneous glycopeptide cancer vaccine candidates.