Chemoenzymatic synthesis of sialylated glycopeptides derived from mucins and T-cell stimulating peptides.
J Am Chem Soc
; 123(45): 11117-25, 2001 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-11697954
ABSTRACT
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-Ser/Thr) and T [Gal 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 beta 1-->3(GlcNAc beta 1-->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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Sialiltransferases
/
Glicopeptídeos
/
Linfócitos T
/
Antígenos Glicosídicos Associados a Tumores
/
N-Acetilglucosaminiltransferases
/
Mucina-1
/
Ácido N-Acetilneuramínico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Suécia