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 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.
Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87, Umeå, Sweden.
Maciej
M
Pudelko
Anna
A
Lindgren
Tobias
T
Tengel
Celso A
CA
Reis
Mikael
M
Elofsson
Jan
J
Kihlberg
D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009077:Mucins / Q000737:chemistry*; D012794:Sialic Acids / Q000737:chemistry*
D006020:Glycopeptides; D007783:Lactones; D009077:Mucins; D012794:Sialic Acids