Inhibition of glycosidases by substituted amidines

Five substituted amidines were examined as reversible inhibitors of glycosidases. All compounds exhibit competitive inhibition. The Ki values of the amidines strongly depend on the hydroxylation pattern and on the structure of the aglycon moeity. Best inhibition (Ki = 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 α-mannosidase and β-glucosidase. The affinity (1/Ki) for α-mannosidase varies with pH indicating that it is the protonated form of the amidine which binds to the enzyme when a enzymic group of pKe = 5.2 is deprotonated.