A drug targeting motif for glycosidase inhibitors: an iminosugar-boronate shows unexpectedly selective b-galactosidase inhibition

Abstract

Boronic acids were tethered to iminosugars in compounds such as 8 and 13 in order to increase their affinity for cell surfaces where glycoprotein processing enzymes are operative. Surprisingly, this modification diminished a-mannosidase inhibition while increasing ߭galactosidase inhibitory activity (8: Ki=2.0ױ0-4 M versus E. coli ߭galactosidase). The presence of a boronate in 8 and 13 has a profound impact on the specificity of this inhibition.