Mucin-type O-
glycans are found on
mucins as well as many other
glycoproteins. The initiation step in synthesis is catalyzed by a large family of
polypeptide GalNAc-
transferases attaching the first
carbohydrate residue, GalNAc, to selected
serine and
threonine residues in
proteins. During the last decade an increasing number of
GalNAc-transferase isoforms have been cloned and their substrate-specificities partly characterized. These differences in substrate specificities have been exploited for in vitro site-directed O-glycosylation. In GlycoPEGylation, polyehylene glycol (PEG) is transferred to recombinant
therapeutics to specific acceptor sites directed by GalNAc-
transferases. GalNAc-
transferases have also been used to control density of glycosylation in the development of
glycopeptide-based
cancer vaccines. The membrane-associated
mucin-1 (MUC1) has long been considered a target for immunotherapeutic and immunodiagnostic measures, since it is highly overexpressed and aberrantly O-glycosylated in most
adenocarcinomas, including breast, ovarian, and
pancreatic cancers. By using
vaccines mimicking the glycosylation pattern of
cancer-cells, it is possible to overcome tolerance in transgenic animals expressing the
human MUC1 protein as a
self-antigen providing important clues for an improved MUC1
vaccine design. The present review will highlight some of the potential applications of site-directed O-glycosylation.