AI Article Synopsis
- The study investigates how different cyclophellitol analogues inhibit three human β-glucosidases (GBA, GBA2, and GBA3).
- N-alkyl cyclophellitol aziridine shows similar potency to its N-acyl counterpart, while the N-sulfonyl version is less effective.
- The findings contribute to existing knowledge and could aid in creating better glycosidase probes that maintain stability in physiological environments.
Article Abstract
The natural product, cyclophellitol and its aziridine analogue are potent mechanism-based retaining β-glucosidase inhibitors. In this paper we explore the inhibitory potency of a number of cyclophellitol analogues against the three human retaining β-glucosidases, GBA, GBA2 and GBA3. We demonstrate that N-alkyl cyclophellitol aziridine is at least equally potent in inhibiting the enzymes evaluated as its N-acyl congener, whereas the N-sulfonyl analogue is a considerably weaker inhibitor. Our results complement the literature on the inhibitory potency of cyclophellitol analogues and hold promise for the future design of more effective activity-based retaining glycosidase probes with respect to probe stability in physiological media.
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