Anomer-selective inhibition of glycosidases using aminocyclopentanols.
[reaction: see text] (1S,2S,3S,4R,5R)-4-amino-5-(hydroxymethyl)cyclopentane-1,2,3-triol 1 is prepared stereoselectively from D-lyxose and displays anomer-selective inhibition for beta-galactosidase (Ki = 3.0 x 10(-6) M) and beta-glucosidase (Ki = 1.5 x 10(-7) M), over alpha-galactosidase (Ki = 2.3 x 10(-5) M) and alpha-glucosidase (IC50 = 1.0 x 10(-4) M). There is no observable cross-reactivity with alpha-mannosidase, beta-mannosidase, or alpha-L-fucosidase.
Leroy
E
E
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
Reymond
J L
JL
D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D007700:Kinetics; D008361:Mannosidases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; C016327:cyclopentanol; D006026:Glycoside Hydrolases; D008361:Mannosidases