Change in specificity of glycosidase inhibition by N-alkylation of amino sugars.
The synthetic amino sugar 1,4-dideoxy-1,4-imino-L-allitol (DIA) is a moderately good inhibitor of human liver alpha-D-mannosidases and a weak inhibitor of alpha-L-fucosidase, N-acetyl-beta-D-hexosaminidase and beta-D-mannosidase. Methylation of the ring nitrogen of DIA markedly decreases the inhibition of all the glycosidases except N-acetyl-beta-D-hexosaminidase. N-Benzylation of DIA essentially abolishes all inhibitory activity, except towards alpha-L-fucosidase, which is more strongly inhibited than by either DIA or N-methyl-DIA. This is the first report of a change of specificity of inhibition of a glycosidase inhibitor by substitution of the ring nitrogen.
al Daher
S
S
Department of Biochemistry, King's College London, U.K.
Fleet
G
G
Namgoong
S K
SK
Winchester
B
B
D001593:Benzyl Compounds / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D050113:Imino Furanoses; D008099:Liver / Q000201:enzymology*; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008745:Methylation; D013402:Sugar Alcohols / Q000378:metabolism*; D043323:alpha-Mannosidase
D001593:Benzyl Compounds; D050113:Imino Furanoses; D013402:Sugar Alcohols; C059190:1,4-dideoxy-1,4-iminoallitol; D006026:Glycoside Hydrolases; D008361:Mannosidases; D043323:alpha-Mannosidase