TOTAL SYNTHESIS OF THE POTENTIAL ANTICANCER VACCINE KH-1 ADENOCARCINOMA ANTIGEN

Human tumours are often marked by the expression of unusual carbohydra te structural motifs(1-3). These carbohydrate domains are manifested a s cell-surface bound glycolipids or glycoproteins(4). 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 sy nthetic compounds(5-7) that mimic cell-surface tumour antigens has alr eady been shown to recognize pertinent human cancer cell lines(8). Fur ther advances in this field depend critically on the availability of t hese tumour-associated carbohydrate antigens which cannot be readily i solated from natural sources in sufficient quantities. Here we present the successful total synthesis of an adenocarcinoma antigen, KH-1, an d of a bioconjugatable analogue which can bind to a carrier protein. T hese results illustrate the capabilities of oligosaccharide synthesis for reconstructing the challenging structural motifs characteristic of carbohydrate antigens, and thereby open up near possibilities for the development of anticancer vaccines.