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Mucin-type O-glycosylation and its potential use in drug and vaccine development.

Abstract
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.
AuthorsMads Agervig Tarp, Henrik Clausen
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1780 Issue 3 Pg. 546-63 (Mar 2008) ISSN: 0006-3002 [Print] Netherlands
PMID17988798 (Publication Type: Journal Article, Review)
Chemical References
  • Cancer Vaccines
  • Mucins
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase
Topics
  • Animals
  • Cancer Vaccines (chemical synthesis, chemistry)
  • Drug Design
  • Glycosylation
  • Humans
  • Mucins (metabolism)
  • N-Acetylgalactosaminyltransferases (metabolism)

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