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

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Johnson, LL
Houston, TA
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2002
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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.

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Tetrahedron Letters

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2002

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43

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Medicinal and biomolecular chemistry

Organic chemistry

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