Kinetic studies on cyclophellitol analogues--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 Ki = 26.9 microM, ki = 0.401 min-1 while the (1R,2S,6S)-diastereoisomer inactivates jack beans alpha-D-mannosidase in a similar manner with Ki = 120 microM, ki = 2.85 min-1. The irreversibility of these compounds was evidenced by the lack of reactivation upon dialysis of the inactivated enzyme.
Tai
V W
VW
Department of Chemistry, Chinese University of Hong Kong, Shatin.
Fung
P H
PH
Wong
Y S
YS
Shing
T K
TK
D003511:Cyclohexanols / Q000737:chemistry* / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043323:alpha-Mannosidase; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors
D003511:Cyclohexanols; D065089:Glycoside Hydrolase Inhibitors; C063285:cyclophellitol; D008361:Mannosidases; D001617:beta-Glucosidase; D043323:alpha-Mannosidase