Chemoenzymatic synthesis of sialylated glycopeptides derived from mucins and T-cell stimulating peptides

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

Authors

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

Journal

Title: Journal of the American Chemical Society

Vol. 123

Pages: 11117-11125

ISSN: 0002-7863

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 69 Citations

Scopus - 66 Citations

Other information

Authenticus ID: P-000-SRV

DOI: 10.1021/ja015570t

Abstract (EN): The Tn, T, sialyl-Tn, and 2,3-sialyl-T antigens are tumor-associated carbohydrate antigens expressed on mucins in epithelial cancers. such as those affecting the breast, ovary, stomach, and colon. Glycopeptides carrying these antigens are of interest for development of cancer vaccines and a short, chemoenzymatic strategy for their synthesis is reported, Building blocks corresponding to the Tn (GalNAc alpha -Scr/Thr) and T [Ga1 beta (1 -->3)GalNAc alpha -Ser/Thr] antigens, which are relatively easy to obtain by chemical synthesis, were prepared and then used in the synthesis of glycopeptides on the solid phase. Introduction of sialic acid to give the 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 is difficult when performed chemically at the building block level. Sialylation was therefore carried out with recombinant sialyltransferases in solution after cleavage of the Tn and T glycopeptides from the solid phase. In the same manner, the core 2 trisaccharide [Gal beta1 -->3(GlcNAc beta1 -->6)GalNAc] was incorporated in glycopeptides containing the T antigen by using a recombinant N-acetylglucosaminyltransferase. The outlined chemoenzymatic approach was applied to glycopeptides from the tandem repeat domain of the mucin MUC1, as well as to neoglycosylated derivatives of a T cell stimulating viral peptide.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9