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Issue 11, 2007
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A potent bicyclic inhibitor of a family 27 α-galactosidase

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Abstract

Two isomeric bicyclo[4.1.0]heptane analogues of the glycosidase inhibitor galacto-validamine, (1R*,2S,3S,4S,5S,6S*)-5-amino-1-(hydroxymethyl)bicyclo[4.1.0]heptane-2,3,4-triol, have been synthesized in 13 steps from 2,3,4,6-tetra-O-benzyl-D-galactose. The inhibitory activities of the two conformationally restricted amines, and their corresponding acetamides, were measured against commercial α-galactosidase enzymes from coffee bean and E. coli. The activity of the glycosyl hydrolase family GH27 enzyme (coffee bean) was competitively inhibited by the 1R,6S-amine (7), a binding interaction that was characterized by a Ki value of 0.541 µM. The GH36 E. coli α-galactosidase exhibited a much weaker binding interaction with the 1R,6S-amine (IC50 = 80 µM). The diastereomeric 1S,6R-amine (9) bound weakly to both galactosidases, (coffee bean, IC50 = 286 µM) and (E. coli, IC50 = 2.46 mM).

Graphical abstract: A potent bicyclic inhibitor of a family 27 α-galactosidase

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Publication details

The article was received on 26 Mar 2007, accepted on 16 Apr 2007 and first published on 30 Apr 2007


Article type: Paper
DOI: 10.1039/B704509C
Org. Biomol. Chem., 2007,5, 1731-1738

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    A potent bicyclic inhibitor of a family 27 α-galactosidase

    Y. Wang and A. J. Bennet, Org. Biomol. Chem., 2007, 5, 1731
    DOI: 10.1039/B704509C

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