The
bleomycins (BLMs) are a family of antitumor
antibiotics used clinically for anticancer
chemotherapy. Their antitumor selectivity derives at least in part from their ability to target
tumor cells, a property that resides in the
carbohydrate moiety of the
antitumor agent. In earlier studies, we have demonstrated that the
tumor cell selectivity resides in the
mannose carbamoyl moiety of the BLM saccharide and that both the BLM
disaccharide and
monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine
dye into cultured
cancer cell lines. Presently, the nature of the participation of the carbamoyl moiety has been explored further to provide compounds of utility for defining the nature of the mechanism of
tumor cell recognition and uptake by BLM saccharides and in the hope that more efficient compounds could be identified. A library of seven
disaccharide-
Cy5**
dye conjugates was prepared that are structural analogues of the BLM
disaccharide. These differed from the natural BLM
disaccharide in the position, orientation, and substitution of the carbamoyl group. Studies of these compounds in four matched sets of
tumor and normal cell lines revealed a few that were both
tumor cell selective and internalized 2-4-fold more efficiently than the natural BLM
disaccharide.