The Tn Antigen-Structural Simplicity and Biological Complexity

• Type of Material: Article
• Authors: Tongzhong Ju, Emory University; Vivianne I. Otto, ETH Zurich; Richard Cummings, Emory University
• Language: English
• Date: 2011-01-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
• Final Published Version (URL): http://dx.doi.org/10.1002/anie.201002313
• Title of Journal or Parent Work: Angewandte Chemie: International Edition
• Volume: 50
• Issue: 8
• Start Page: 1770
• End Page: 1791
• Grant/Funding Information: This work was supported by an NIH RO1 grant (RO1 GM068559) to R.D.C. and by an NIH RO1 grant (RO1K80876) to T.J.
• Keywords: L-selectin ligand; Human transferin receptor; Physical Sciences; Solid phase synthesis; Human immunodeficiency virus (HIV); chaperone proteins; mucins; carbohydrates; antigens; O-linked glycosylation; Breast cancer cells; Chemistry; Galactosamine specific lectins; Chemistry, Multidisciplinary; Science & Technology; transferases
• Research Categories: Engineering, Biomedical; Health Sciences, Pharmacy; Chemistry, Pharmaceutical; Chemistry, Biochemistry

Abstract

Glycoproteins in animal cells contain a variety of glycan structures that are added co- and/or posttranslationally to proteins. Of over 20 different types of sugar-amino acid linkages known, the two major types are N-glycans (Asn-linked) and O-glycans (Ser/Thr-linked). An abnormal mucin-type O-glycan whose expression is associated with cancer and several human disorders is the Tn antigen. It has a relatively simple structure composed of N-acetyl-D- galactosamine with a glycosidic αlinkage to serine/threonine residues in glycoproteins (GalNAcα1-O-Ser/Thr), and was one of the first glycoconjugates to be chemically synthesized. The Tn antigen is normally modified by a specific galactosyltransferase (T-synthase) in the Golgi apparatus of cells. Expression of active T-synthase is uniquely dependent on the molecular chaperone Cosmc, which is encoded by a gene on the X chromosome. Expression of the Tn antigen can arise as a consequence of mutations in the genes for T-synthase or Cosmc, or genes affecting other steps of O-glycosylation pathways. Because of the association of the Tn antigen with disease, there is much interest in the development of Tn-based vaccines and other therapeutic approaches based on Tn expression. An abnormal sugar: The expression of the abnormal O-glycan called Tn antigen (see structure) in animal glycoproteins typically represents a disease condition. This Review discusses a broad range of chemical and biological studies on the Tn antigen that could lead to new diagnostics and therapeutics.