Multivalent
iminosugars have recently emerged as powerful tools
to inhibit the activities of specific glycosidases. In this work,
biocompatible dextrans were coated with iminosugars to form linear
and ramified polymers with unprecedently high valencies (from 20 to
900) to probe the evolution of the multivalent inhibition as a function
of ligand valency. This study led to the discovery that polyvalent
iminosugars can also significantly enhance, not only inhibit, the
enzymatic activity of specific glycoside-hydrolase, as observed on
two galactosidases, a fucosidase, and a bacterial mannoside phosphorylase
for which an impressive 70-fold activation was even reached. The concept
of glycosidase activation is largely unexplored, with a unique recent
example of small-molecules activators of a bacterial O-GlcNAc hydrolase.
The possibility of using these polymers as “artificial enzyme
effectors” may therefore open up new perspectives in therapeutics
and biocatalysis