INHIBITION OF GLYCOSIDASES BY SUBSTITUTED AMIDINES

Five substituted amidines were examined as reversible inhibitors of glycosidases. All compounds exhibit competitive inhibition. The K-i values of the amidines strongly depend on the hydroxylation pattern and on the structure of the aglycon moeity. Best inhibition (K-i = 10(-6)-10(-7)M) were observed with structures that closely resemble to sugar structure. The pH dependence of a particular potent inhibitor was also examined on alpha-mannosidase and beta-glucosidase. The affinity (1/K-i) for alpha-mannosidase varies with pH indicating that it is the protonated form of the amidine which binds to the enzyme when a enzymic group of pK(e) = 5.2 is deprotonated.