Chemoenzymatic synthesis of derivatives of a T-cell-stimulating peptide which carry tumor-associated carbohydrate antigens

• Type: Article in International Scientific Journal
• Date: 2001

Authors

George, SK (Author) Other; Holm, B (Author) Other; Celso Reis (Author) Other; Schwientek, T (Author) Other; Clausen, H (Author) Other; Kihlberg, J (Author) Other

Journal

Title: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1

Pages: 880-885

ISSN: 1472-7781

Publisher: ROYAL SOC CHEMISTRY

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-000-XE7

DOI: 10.1039/b009567m

Abstract (EN): The Tn (GalNAc alpha -Ser/Thr), T [Gal beta (1 -->3)GalNAc alpha -Ser/Thr], sialyl-Tn [Neu5Ac alpha (2 -->6)GalNAc alpha -Ser/Thr] and 2,3-sialyl-T [Neu5Ac alpha (2 -->3)Gal beta (1 -->3)GalNAc alpha -Ser/Thr] antigens are examples of tumor-associated carbohydrate antigens expressed by epithelial cancers. We now describe the preparation of 2-bromoethyl glycosides corresponding to the Tn and T antigens in one and five chemical steps (51 and 15% total yield), respectively, starting from N-acetylgalactosamine. The 2-bromoethyl Tn and T glycosides were used to alkylate a homocysteine residue incorporated in a peptide that is able to bind to class I MHC molecules on antigen-presenting cells. The two neoglycopeptides were then converted into glycopeptides which carry the sialyl-Tn and 2,3-sialyl-T antigens by using recombinant sialyltransferases. Interestingly, the sialyltransferases were able to sialylate the Tn and T carbohydrate moieties even though they were linked to the peptide backbone via a spacer instead of being attached to serine or threonine. The four glycopeptides will be used in studies directed towards inducing a carbohydrate-specific T cell response against the Tn, T, sialyl-Tn, and 2,3-sialyl-T antigens.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6