W. B. Gruhn, M. L. Bender
Sep 1, 1974
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0
Influential Citations
18
Citations
Journal
Bioorganic Chemistry
Abstract
Abstract The N -methylacetohydroxamic acid group has been introduced into cyclohexaamylose by the following sequence of reactions: (1) carboxymethylation of cyclohexaamylose by iodoacetic acid, (2) methylation of carboxymethylcyclohexaamylose with diazomethane, and (3) reaction of the carboxymethylcyclohexaamylose methyl ester with N -methylhydroxylamine to form the N -methylacetohydroxamic acid-substituted cyclohexaamylose. By employing purification procedures involving ionexchange chromatography, the synthesis yielded a mono-substituted cyclohexaamylose- N -methylacetohydroxamic acid with selective modification of the C-2, C-3 hydroxyl group side of the cyclohexaamylose ring. p -Nitrophenyl acetate and 2-hydroxy-5-nitro-α-toluenesulfonic acid sultone react 20- and 70-fold faster with cyclohexaamylose- N -methylacetohydroxamic acid than with N -methylmethoxyacetohydroxamic acid. Cyclohexaamylose- N -methylacetohydroxamic acid also displays a marked kinetic stereospecificity for p -nitroover m -nitrophenyl acetate (whereas cyclohexaamylose itself exhibits the reverse stereospecificity). These reactions were shown to be competitively inhibited by cyclohexanol. This evidence indicates that cyclohexaamylose- N -methylacetohydroxamic acid binds the substrate in a reversible complexation step prior to nucleophilic attack and thus is an enzyme model.