Binding and stabilisation effects of glycodendritic compounds with peanut agglutinin.

A number of new polyhydroxy-dendritic structures have been constructed from a few basic modules. The cores were derived from N-tert(butyloxycarbonyl)tris[(propargyloxy)methyl]aminomethane, N,N'-bis-1,3-(tris-(propargyloxymethyl)methyl)-5-(hydroxymethyl)isophthalamide, and N,N',N″-tris-1,3,5-(tris-(propargyloxymethyl)methyl)-1,3,5-benzene tricarboxamide while the terminal groups were derived from β-azido-galactose and β-azido-lactose leading to six new glycodendrimeric compounds with up to 63 hydroxyl groups on the periphery. The binding ability of the new compounds to peanut agglutinin (PNA), a galactose recognizing lectin from Arachis hypogaea, was investigated by nano-Isothermal Titration Calorimetry and nano-Differential Scanning Calorimetry. We found that the compounds had stronger stabilising effect on the macromolecules compared to the corresponding sugars. The interaction between lectin and the glycodendrimeric unit is entropically driven with only a low enthalpic contribution. A trend was found with increasing number of carbohydrates that is strongly influenced by the steric constraints of the ligands. Our results indicate the significance of multivalency and size control in the successful design of lectin inhibitors.