Oligosaccharide epitope diversity and therapeutic potential

In the search for new therapeutics based on oligosaccharide-protein interactions (glycotherapeutics) several unique features about glycans must be borne in mind; i.e., their structural diversity; the recognition of epitopes on branched sequences with local conformation; and, multivalent presentation. These characteristics are variously important in, for example, the potential exploitation of a) high affinity interactions of glycosaminoglycans (proteoglycan oligosaccharides) with proteins, b) monoclonal antibody, mammalian lectin and microorganism recognition of mucin-type oligosaccharides, and c) the functions of both lipid-linked oligosaccharides (glycolipids) and glycoproteins (GPI anchored). In the first, diverse sequence determinants (reviewed in Hounsell, 1994; Hounsell, 1995; Hounsell and Bailey, 1997) tend to be displayed at multiple sites along a linear polymer; in the second a high degree of peptide substitution and oligosaccharide branching leads to crowding of potential ligands (Hounsell et al., 1996); and, in the last, cooperativity may involve lipid-lipid, oligosaccharide-oligosaccharide and oligosaccharide-protein mediated clustering. These different strategies of nature can be explored by NMR spectroscopy of functional motifs modelled by computer graphics in the context of multi-component macromolecular systems (Hounsell, 1994; 1995).