Solid-Phase Synthesis of Glycopeptides: Immunological Studies with T Cell Stimulating Glycopeptides

Abstract

Stepwise solid-phase synthesis using glycosylated amino acids as puilding blocks has been shown to be the most general and efficient approach for preparation of glycopeptides. The a-amino group of the glycosylated amino acids should be protected with the fluoren-9-ylmethoxy­ carbonyl (Fmoc) group whereas acetyl groups, or acid labile protective groups, are suitable for the carbohydrate hydroxyl groups. Due to the recent rapid development of Fmoc solid-phase glycopeptide synthesis glycopeptides are increasingly being made available for investigations in biological sciences, such as studies of the cellular immune response to glycopeptides. These studies have established that glycopeptides are bound well by both class I and . II MHC molecules and elicit a carbohydrate specific T cell response after immunization, provided that the position for the glycan is chosen carefully in the centre of the peptide. Such a location most likely allows contacts between carbohydrate and the CDR3s of the T cell receptor. Investigations using viral glycoproteins suggest that the large N-linked glycans influence the T cell response to glycoproteins, but that this does not involve specific interactions between the glycan and the T cell. Furthermore, viruses seem to exploit mutations which introduce or delete N-linked glycans to escape from attack by T cells. In contrast, studies have revealed that the smaller 0-linked carbohydrates found on collagen or mucins are able to elicit a carbohydrate specific T cell response. Altogether, these immunological studies have suggested novel applications in medicine, including generation of a cellular immune response to carbohydrate antigens found on pathogens or tumour cells, and induction of tolerance in autoimmune rheumatoid arthritis.