Bacterial P-glucosidase

The a-5-C-(l,3-dihydroxybutyl) derivative of hyacinthacine Ai 18 was reported to be a good inhibitor of yeast a-glucosidase and bacterial p-glucosi-dase, whereas 19 with the additional OH on the side chain, is a weaker inhibitor of the both enzymes. Alkaloid 25, regarded as a 5-C-(3-hydroxybutyl) derivative of A2, exhibits no activity, indicating that this long side chain plays an important role in the inhibition of the compounds (Table 1). 

Table 13.2 presents a head-to-head comparison of GBA-specific probe 7 and aziridine 13 [20]. As expected, aziridine 13 labels all four murine retaining P-exoglucosidases depending on their expression in various tissues. As is the case with epoxide 7, aziridine 13 is both cell permeable and tissue permeable and both probes are therefore amenable for in vivo labeling experiments. The question why GBA, but not the other enzymes, accepts (and, in fact, prefers) a bulky substituent at C6 remains unanswered. However, both probes react with a considerable number of bacterial glucosidases, some of which appear to have evolved from endoglu-cosidases and it might well be that GBA is evolutionary related to these bacterial enzymes [20]. 

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