Total synthesis of the potential anticancer vaccine KH-1 adenocarcinoma antigen

Human tumours are often marked by the expression of unusual carbohydrate structural motifs. These carbohydrate domains are manifested as cell-surface bound glycolipids or glycoproteins. This raises the possibility of using cell-free equivalents of these domain compounds, obtained by total synthesis with a view towards triggering some level of immune response. In fact, the serum of mice immunized with fully synthetic compounds that mimic cell-surface tumour antigens has already been shown to recognize pertinent human cancer cell lines. Further advances in this field depend critically on the availability of these tumour-associated carbohydrate antigens which cannot be readily isolated from natural sources in sufficient quantities. Here we present the successful total synthesis of an adenocarcinoma antigen, KH-1, and of a bioconjugatable analogue which can bind to a carrier protein. These results illustrate the capabilities of oligosaccharide synthesis for reconstructing the challenging structural motifs characteristic of carbohydrate antigens, and thereby open up new possibilities for the development of anticancer vaccines.