Glycoside hydrolases inhibition

F. Marcelo, Y. He, S. A. Yuzwa, L. Nieto, J. Jimenez-Barbero, M. Sollogoub, D. J. Vocadlo, G. D. Davies, and Y. Bleriot, Molecular basis for inhibition of GH84 glycoside hydrolases by substituted azepanes Conformational flexibility enables probing of substrate distortion, J. Am. Chem. Soc., 131 (2009) 5390-5392. 

An ethyl acetate extract of Sicilian sumac inhibited alpha-amylase, a glycoside hydrolase, indicating hypoglycemic activity of this extract. The IC50 was 28.7 jig/ml (Giancarlo et al. 2006). 

Maltosylamine has proved to be an effective specific inhibitor of sweet potato /3-amylase.This result extends the observation that 1-aminoglycosides are specific inhibitors of glycoside hydrolases, and also demonstrates that enzymes acting with inversion, as well as those acting with retention, of anomeric configuration can be inhibited by glycosylamines. /3-Maltosylamine, which acted as a reversible inhibitor, appeared to be directed to the active-site... 

Normal human serum contains at least three forms of a-o-mannosidase an acidic form which has a pH optimum of 4.25, is inhibited by Co + and is thermostable an intermediate form, which has a pH optimum of 5.6—5.7, is stimulated by Co + and is heat labile at 50 °C and a neutral form (pH optimum 6.0—6.5). In cases of mucolipidosis II and III the serum acidic activity persists while the intermediate activity is absent or altered. Heating the serum does not affect the pH-activity curve, the electrofocusing profile or the response to Co + of the enzyme. The absent or altered intermediate a-D-mannosidase may be responsible for aberrant biochemical properties reported for other glycoside hydrolases in mucolipidosis II and III. 

In the classic studies by Sharon et al. [12] and Legler and Bause [13], epoxyalkyl glycosides were used to inhibit the action of various glycan hydrolases. In view of the almost certain presence of an acid residue at the active site and the two mechanisms which have been proposed for the action of glycan hydrolases, namely that involving hydrolysis with retention or inversion of configuration at the anomeric centre (Figs. 1 and 2) [14, 15], we decided to use epoxyalkyl... 

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