Kinetic-Studies on Cyclophellitol Analogs - Mechanism-Based Inactivators

The (1R,6S)- and (1R,2S,6S)-diastereoisomers of cyclophellitol were found to be effective irreversible inactivators of α-D-glucosidase and α-D-mannosidase, respectively. The (1R,6S)-diastereoisomer inactivates brewers yeast α-D-glucosidase according to pseudo-first order kinetics with inactivation constants of K_i = 26.9 μM, k_i = 0.401 min^-1 while the (1R,2S,6S)-diastereoisomer inactivates jack beans α-D-mannosidase in a similar manner with K_i = 120 μM, k_i = 2.85 min^-1. The irreversibility of these compounds was evidenced by the lack of reactivation upon dialysis of the inactivated enzyme.