348145-67-5Relevant academic research and scientific papers
Chemoenzymatic synthesis of derivatives of a T-cell-stimulating peptide which carry tumor-associated carbohydrate antigens
George,Holm,Reis,Schwientek,Clausen,Kihlberg
, p. 880 - 885 (2001)
The Tn (GalNAcα-Ser/Thr), T[Galβ(1→3)GalNAcβ-Ser/Thr], sialyl-Tn[Neu5Acα(2→6)GalNAcα-Ser/Thr] and 2,3-sialyl-T[Neu5Acα(2→3)Galβ(1→3)GalNAcα-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.
Chemoenzymatic synthesis of sialylated glycopeptides derived from mucins and T-cell stimulating peptides
George,Schwientek,Holm,Reis,Clausen,Kihlberg
, p. 11117 - 11125 (2007/10/03)
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 interestfor development of cancer vaccines and a short, chemoenzymatic strategy for their synthesis is reported. Building blocks corresponding to the Tn (Ga1NAcα-Ser/Thr) and T [Galβ(1→3)Ga1NAcα-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 [Neu5Acα(2→6)Ga1NAcα-Ser/Thr] and 2,3-sialyl-T [Neu5Acα(2→3)Ga1β(1→3)Ga1NAcα-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 [Ga1β1→3(G1cNAcβ1→6)Ga1NAc] 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 MUCl, as well as to neoglycosylated derivatives of a T cell stimulating viral peptide.
