Inhibition of beta-glycosidases by acarbose analogues containing cellobiose and lactose structures.
Acarbose analogues, containing cellobiose and lactose structures, were prepared by reaction of the two disaccharides with acarbose and Bacillus stearothermophilus maltogenic amylase. The kinetics for the inhibition by the two analogues was studied for beta-glucosidase, beta-galactosidase, cyclomaltodextrin glucanosyltransferase (CGTase), and alpha-glucosidase. Both analogues were potent competitive inhibitors for beta-glucosidase, with K(I) values in the range of 0.04-2.44 microM, and the lactose analogues were good uncompetitive inhibitors for beta-galactosidase, with K(I) values in the range of 159-415 microM, while acarbose was not an inhibitor for either enzyme at 10 and 5 mM, respectively. Both analogues were also potent mixed inhibitors for CGTase, with K(I) values in the range of 0.1-9.3 microM. The lactose analogue was a 6.4-fold better competitive inhibitor for alpha-glucosidase than was acarbose.
Lee
S B
SB
Laboratory of Carbohydrate Chemistry and Enzymology, Iowa State University, Ames 50011, USA.
Park
K H
KH
Robyt
J F
JF
D020909:Acarbose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000681:Amylases / Q000037:antagonists & inhibitors; D002240:Carbohydrate Sequence; D002475:Cellobiose; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D007785:Lactose; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D002475:Cellobiose; D005964:Glucosyltransferases; C019963:cyclomaltodextrin glucanotransferase; D000681:Amylases; D006026:Glycoside Hydrolases; D001617:beta-Glucosidase; D001616:beta-Galactosidase; D007785:Lactose; D020909:Acarbose