Glycopeptide synthesis and the effects of glycosylation on protein structure and activity

Despite the omnipresence of protein glycosylation in nature, little is know n about how the attachment of carbohydrates effects peptide and protein act ivity. One reason is the lack of a straightforward method to access biologi cally relevant glycopeptides and glycoproteins. The isolation of homogeneou s glycopeptides from natural sources is complicated by the heterogeneity of naturally occuring glycoproteins. It is a chemical and chemoenzymatic synt hesis that is meeting the challenge to solve this availability problem, thu s playing a key role for the advancement of glycobiology. The current art o f glycopeptide synthesis, albeit far from being routine, has reached a leve l of maturity that allows for the access to homogeneous and pure material f or biological and medicinal research. Even the ambitious goal of the total synthesis of an entire glycoprotein is within reach. It is demonstrated tha t with the help of synthetic glycopeptides the effects of glycosylation on protein structure and function can be studied in molecular detail. For exam ple, in immunology, synthetic (tumour-specific) glycopeptides can be used a s immunogens to elicit a tumour-cell-specific immune response. Again, synth etic glycopeptides are an invaluable tool to determine the fine specificity of the immune response that can be mediated by both carbohydrate-specific B and T cells. Furthermore, selected examples for the use of synthetic glyc opeptides as ligands of carbohydrate-binding proteins and as enzyme substra tes or inhibitors are presented.