OLIGOSACCHARIDES RELATED TO TUMOR-ASSOCIATE ANTIGENS .3. SYNTHESIS OFTHE PROPYL GLYCOSIDES OF THE TRISACCHARIDE A-D-GALP-(1-]3)-BETA-D-GALPNAC-(1-]3)-ALPHA-D-GALP AND OF THE TETRASACCHARIDE -D-GALP-(1-]3)-BETA-D-GALPNAC-(1-]3)-ALPHA-D-GALP, COMPONENTS OF A TUMOR-ANTIGEN RECOGNIZED BY THE ANTIBODY MBR1

The synthesis of the trisaccharide P-D-Galp-(1 --> 3)-beta-D-GalpNAc-( l --> 3)-alpha-D-Galp-l-OPr (2) and of the tetrasaccharide alpha-L-Fuc p-(1 --> 2)-beta-D-Galp-(1 --> 3)-beta-D-Galp (3), starting from the d isaccharidic dihydrooxazole donor 5, is described. Glycosylation of 5 with 6 in the presence of Me(3)SiOTf gave the trisaccharide 7 which wa s deprotected with standard methods to give, via 8, compound 2 (Scheme I). Alternatively, protection of 8 as the 4',6'-O-benzylidene derivat ive 9 followed by glycosylation with 10 and by standard deprotection a fforded the tetrasaccharide 3 (Scheme 2). Biological testing showed th at trisaccharide 2 is unable to inhibit the binding of the monoclonal antibody MBr1 to the target tumor cells MCF7, while tetrasaccharide 3 inhibits the binding in ca. 7-fold extent with respect to the previous ly tested trisaccharide alpha-L-Fucp-(1 --> 2)-beta-DGalp-(1 --> 3)-be ta-D-GalpNAc-1-OPr. These results indicate that the galactose correspo nding to the unit D of compound 1 plays an important role in; defining the MBrl-recognized epitope and confirm the essential role of fucose for MAb recognition.