Pp. Deshpande et Sj. Danishefsky, TOTAL SYNTHESIS OF THE POTENTIAL ANTICANCER VACCINE KH-1 ADENOCARCINOMA ANTIGEN, Nature, 387(6629), 1997, pp. 164-166
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.