Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Biochimica et Biophysica Acta - General Subjects |
| Vol/bind | 1780 |
| Udgave nummer | 3 |
| Sider (fra-til) | 546-563 |
| Antal sider | 17 |
| ISSN | 0304-4165 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
Keywords: Animals; Cancer Vaccines; Drug Design; Glycosylation; Humans; Mucins; N-AcetylgalactosaminyltransferasesAdgang til dokumentet
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I: Biochimica et Biophysica Acta - General Subjects, Bind 1780, Nr. 3, 2007, s. 546-563.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Mucin-type O-glycosylation and its potential use in drug and vaccine development
AU - Tarp, Mads Agervig
AU - Clausen, Henrik
N1 - Keywords: Animals; Cancer Vaccines; Drug Design; Glycosylation; Humans; Mucins; N-Acetylgalactosaminyltransferases
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1016/j.bbagen.2007.09.010
DO - 10.1016/j.bbagen.2007.09.010
M3 - Journal article
C2 - 17988798
SN - 0304-4165
VL - 1780
SP - 546
EP - 563
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -