Formation of lactones from sialylated MUC1 glycopeptides

The tumor-associated carbohydrate antigens TN, T, sialyl TN and sialyl T are expressed on mucins in several epithelial cancers. This has stimulated studies directed towards development of glycopeptide-based anticancer vaccines. Formation of intramolecular lactones involving sialic acid residues and...

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Published in:Organic & biomolecular chemistry 2006-02, Vol.4 (4), p.713-720
Main Authors: Pudelko, Maciej, Lindgren, Anna, Tengel, Tobias, Reis, Celso A, Elofsson, Mikael, Kihlberg, Jan
Format: Article
Language:English
Subjects:
Glycopeptides - chemistry
Glycopeptides - metabolism
Glycopeptides/chemistry/metabolism
Hydrolysis
Lactones - chemical synthesis
Lactones - chemistry
Lactones/chemical synthesis/chemistry
Magnetic Resonance Spectroscopy
Molecular Structure
Mucins - chemistry
Sialic Acids - chemistry
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Summary:The tumor-associated carbohydrate antigens TN, T, sialyl TN and sialyl T are expressed on mucins in several epithelial cancers. This has stimulated studies directed towards development of glycopeptide-based anticancer vaccines. Formation of intramolecular lactones involving sialic acid residues and suitably positioned hydroxyl groups in neighboring saccharide moieties is known to occur for glycolipids such as gangliosides. It has been suggested that these lactones are more immunogenic and tumor-specific than their native counterparts and that they might find use as cancer vaccines. We have now investigated if lactonization also occurs for the sialyl TN and T antigens of mucins. It was found that the model compound sialyl T benzyl glycoside , and the glycopeptide Ala-Pro-Asp-Thr-Arg-Pro-Ala from the tandem repeat of the mucin MUC1, in which Thr stands for the 2,3-sialyl-T antigen, lactonized during treatment with glacial acetic acid. Compound gave the 1''--> 2' lactone as the major product and the corresponding 1''--> 4' lactone as the minor product. For glycopeptide the 1''--> 4' lactone constitued the major product, whereas the 1''--> 2' lactone was the minor one. When lactonized was dissolved in water the 1''--> 4' lactone underwent slow hydrolysis, whereas the 1''--> 2' remained stable even after a 30 days incubation. In contrast the corresponding 2,6-sialyl-TN glycopeptide did not lactonize in glacial acetic acid.
ISSN:1477-0520
1477-0539
1477-0539
DOI:10.1039/b514918e