Chemoenzymatic Synthesis and Lectin Binding Properties of Dendritic N-Acetyllactosamine

Proof that multivalency amplifies individual carbohydrate−protein interactions is growing. N-Acetylglucosamine (GlcNAc)-based dendrimers with valencies of two (9), four (10), and eight (11) were prepared in fair to excellent yields (65−99%) on the basis of the rational scaffolding of l-lysine on solid phase using established Fmoc and HOBt chemistry. These GlcNAc dendrimers were then further transformed enzymatically (79−90% yields) into dendritic N-acetyllactosamine (LacNAc) derivatives [di- (12), tetra- (13), and octavalent (14)] using UDPglucose, UDP-glucose 4‘-epimerase, and GlcNAc β-1,4-galactosyltransferase. GlcNAc and LacNAc dendrimers were used to inhibit lectin−porcine stomach mucin interactions. Wheat germ agglutinin and Erythrina cristagalli lectin were used for GlcNAc and LacNAc dendrimers, respectively. Di-, tetra-, and octavalent GlcNAc dendrimers exhibited IC50s of 3100, 509, and 88 μM (6200, 2040, and 703 μM, with respect to monomeric GlcNAc content). IC50s for the LacNAc series were 341, 143, and 86 μM (682, 574, and 692 μM, as compared with monomeric LacNAc content). These data represent more than 20-fold increases in inhibitory potential for dendritic GlcNAc as compared to that for monomeric GlcNAc. Studies with E. cristagalli do not reveal significant increased inhibitory potential with multivalency.