Glycopeptides and glycoproteins: Focus on the glycosidic linkage

This review has aimed to showcase research which has enlightened us about the structure of naturally occurring glycopeptides, and those contributions which have led to the chemical synthesis of glycopeptides. By focussing discussion around the key linkage between the carbohydrate and the peptide/protein, it has been possible to draw information together in a new way. The more global strategic issues regarding assembly of the carbohydrate and peptide portions of the molecules, have not been contemplated. This has been done well elsewhere, and has made it possible to consider the unique structural features of this class of molecules which set them apart from either carbohydrates or peptides. It might have been exacted that enzymes would have been featured in section 3, but alas, enzymes have been covered in this review only to the extent that they have been used to remove protecting groups under mild, selective conditions. The expression 'enzymatic glycoprotein synthesis' is used widely, but the use of enzymes is invariably restricted to the formation of glycosidic linkages between sugar units. Little is known about the enzymes which catalyze the formation of the key glycosidic linkages between the carbohydrate and the peptide. An exception to this is oligosaccharyl transferase, which has been isolated and studied. Perhaps the isolation, characterization and application of these glycosyl transferases is a future direction in the field of glycopeptides. It might well be asked why nature employs different kinds of glycosidic linkages in different glycopeptides. Is it related to the environment in which the protein has to perform? Is it related to the tasks that the protein has to perform? Is it related to the kinds of modifications that the glycoprotein undergoes during its lifetime? These, and many more questions, remain to be answered. A key tool in addressing them will undoubtedly be the study of synthetic compounds in biological systems. While it is now possible to assemble glycopeptides of some complexity, it must be recognized that this work is being done by a relatively small group of highly specialized organic chemists. The chemistry is plagued by the nuances of both carbohydrate and peptide chemistry. Much work has yet to be done in the development of general methods for the construction of glycosidic linkages between carbohydrates and peptides.