ENZYME-ASSISTED SYNTHESIS OF A BIVALENT HIGH-AFFINITY DODECASACCHARIDE INHIBITOR OF MOUSE GAMETE ADHESION - THE LENGTH OF THE CHAINS CARRYING DISTAL ALPHA-1,3-BONDED GALACTOSE RESIDUES IS CRITICAL

Proposing to study the molecular mechanisms of mouse gamete adhesion w ith the aid of high affinity adhesion inhibitors of saccharide nature, we report here the enzymatic synthesis of a bivalent oligosaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3(Ga l alpha 1-3Gal beta 1-4GlcNAc beta 1- 3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (4), consisting of two long arms that link together tw o distal alpha 1,3-galactose residues. Binding data reported elsewhere (E. Litscher et al., Biochemistry, 1995, 34, 4662-4669) show that 4 i s a high affinity inhibitor of mouse gamete adhesion in vitro (IC50 = 9 mu M), while a related octasaccharide Gal alpha 1-3Gal beta 1-4GlcNA c beta 1-3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc , consisting of two short arms is of very low inhibitory activity. The data highlight the importance of the two alpha-galactose residues of 4, and the length of the sugar chains joining them.