Glycosidases mechanism-based

The terminal fluoroolefine group is a useful functionality in the design of mechanism-based enzyme inhibitors [29]. The defluorinative formation of quinone methide intermediates (82) from 80 and their trapping of active enzyme has been proposed as a method for affinity labeling of (3-glycosidases as shown in Scheme 6.16 [30]. 

Some of the more reactive irreversible inhibitors have been variously called suicide substrates, koa inhibitors, and mechanism-based inhibitors. These compounds are relatively innocuous substrate analogs until converted by the enzyme to highly reactive products capable of covalent attachment at the active site. Since the enzyme mechanism is involved, the covalently conjugated amino acid is often directly involved in catalysis. There has recently been increased interest in mechanism-based glycosidase inhibitors because of their value in studying the reaction mechanism (4, 48) and in their potential therapeutic application 47). 

Figure 21 Chemical probes for monitoring glycan-processing enzymes, (a) Mechanism-based probe for labeling active exo-glycosidases in cell lysates/ (b) FRET-based reporter for OGT activity in cells. ...

The presence of such enolic ions in alkaline solutions of sugars was shown later by Isbell et al. (67). The mechanism of the alkaline -elimination reaction of substituted serine and threonine glycosidases based on this concept is shown in Figure 9. 

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