Synthetic glycopeptides for the development of tumour-selective vaccines.
Based on structural information reported for the tumour-associated epithelial mucin MUC1, glycopeptides have been synthesized which contain tumour-associated saccharide antigens. such as the Thomsen-Friedenreich (T), TN or sialyl TN antigen. in combination with peptide sequences of the tandem repeat region of MUC1. Solid-phase syntheses have been carried out using N-Fmoc protected O-glycosyl serine and threonine building blocks and an allylic anchor which is stable to basic and acidic conditions, but can be cleaved under neutral conditions in a palladium(0)-catalysed allyl transfer reaction. In addition. a (2-3)sialyl T antigen threonine building block was prepared by a chemoenzymatic strategy and used in the synthesis of an N-terminal glycopeptide antigen of leukosialin (CD43). The proliferation of cytotoxic T cells could be induced using a construct consisting of a MUC1-glycopeptide antigen and a T cell epitope.
Kunz
Horst
H
Institut fuer Organische Chemie, Johannes Gutenberg-Universitaet Mainz, D-55099 Mainz, Germany. hokunz@uni-mainz.de
D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000138:chemical synthesis*; D002240:Carbohydrate Sequence; D004848:Epithelium / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis*; D006021:Glycophorins / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018396:Mucin-1 / Q000737:chemistry
D019496:Cancer Vaccines; D006020:Glycopeptides; D006021:Glycophorins; D008562:Membrane Glycoproteins; D018396:Mucin-1