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 alpha-D-glucosidase and alpha-D-mannosidase, respectively. The (1R,6S)-diastereoisomer inactivates brewers yeast alpha-D-glucosidase according to pseudo-first order kinetics with inactivation constants of K-i = 26.9 mu M, k(i) = 0.401 min(-1) while the (1R,2S,6S)-diastereoisomer inactivates jack beans alpha-D-mannosidase in a similar manner with K-i = 120 mu M, k(i) = 2.85 min(-1). The irreversibility of these compounds was evidenced by the lack of reactivation upon dialysis of the inactivated enzyme. (C) 1995 Academic Press, Inc.