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

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 beta-galactosidase inhibitory activity (8: K-i = 2.0 x 10(-4) M versus E. coli beta-galactosidase). The presence of a boronate in 8 and 13 has a profound impact on the specificity of this inhibition. (C) 2002 Elsevier Science Ltd. All rights reserved.