Synthesis of Lactose Dendrimers and Multivalency Effects in Binding to the Cholera Toxin B Subunit

The synthesis of lactose-containing dendrimers is described; the dendrimers used were based on the 3,5-di(2-aminoethoxy)benzoic acid repeating unit. Dendrimers of generation 1, 2, and 3 − containing 2, 4, and 8 endgroups, respectively − were used. These were coupled to lactose isothiocyanate, resulting in thiourea-linked glycodendrimers, characterized by 13C NMR and mass spectrometry. The lactose-functionalized dendrimers were evaluated by fluorescence assay for their ability to bind to the cholera toxin B subunit. Binding affinities determined in the fluorescence assay (Kd’s) ranged from 18 mM for monovalent lactose to 33 μM for an octavalent lactose dendrimer.