Mass spectrometry (MS) has played a major role in structural characterization of oligosaccharides and contributed to carbohydrate ligand assignments. Analyses of oligosaccharides and the lipid-linked oligosaccharide probes by MS are integral parts of our overall strategy for assignments of specificities of carbohydrate-protein interactions. We have developed various MS-based methods for sequencing neutral and acidic (including sialylated and sulphated) oligosaccharides. The use of negative-ion detection has been particularly important, e.g. negative-ion electrospray ionisation (ESI)-MS for profiling of heparin oligosaccharides, negative-ion ESI-CID-MS/MS for sequencing, branching pattern analysis, and backbone chain and blood-group typing of neutral and acidic oligosaccharides, and linkage assignment of glucan oligosaccharides in linear ‘homo’ and ‘hetero’, and branched sequences. The method for in-situ high-performance TLC-MS in conjunction with solid-phase ligand binding experiments has been a means of oligosaccharide ligand discovery.

The applications have included sequence assignments of sulphated oligosaccharide ligands for E-selectin; the cysteine-rich region of the macrophage endocytosis receptor; the discovery of ‘yeast-type’ O-mannosyl glycans and their high prevalence in the mammalian brain, now known to be defective in certain congenital neuromuscular diseases; a novel non-sulphated and non-acetylated glucosamine-containing heparin-associated tetrasaccharide sequence as the prion antigen (10E4) in the nervous system; structural motifs of under-sulphated chondroitin sulphate A and hyaluronic acid chains as mediators of the adhesion of Plasmodium falciparum-infected erythrocytes; construction of a ‘glucome’ microarray and its use in detection and specificity assignment of glucan interactions with antibodies, carbohydrate-binding modules, and signalling molecules of the immune system against pathogens; and many novel oligosaccharide sequences from glycoproteins, glycolipids, glycosaminoglycans and polysaccharides of biological interests.