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- p-(Bromoacetamido)phenyl uridyl pyrophosphate: an active-site-directed irreversible inhibitor for uridine diphosphate galactose 4-epimerase
- By Wong, Yun-Hua Huang; Winer, Fredric B.; Frey, Perry A. From Biochemistry (1979), 18(24), 5332-6. Language: English
The synthesis of p-(bromoacetamido)phenyl uridyl pyrophosphate (I) is described. This compd. was an active-site-directed irreversible inhibitor of Escherichia coli UDP-galactose 4-epimerase. The inactivation followed pseudo-first-order kinetics at pH 8.5 in nonnucleophilic buffers, and a satn. effect was seen in the pseudo-first-order rate const. as the concn. of I was increased. The half-satn. parameter for I in the inactivation was 0.21 mM, which compared favorably with the inhibition const. of 0.3 mM for I acting as a competitive reversible inhibitor of the enzyme. The inactivation rate was slow, with a min. half-time of 12 h at pH 8.5 and 27°. Both specific and nonspecific alkylation by I occurred but the nonspecific alkylation was faster than the inactivation and the rate of inactivation correlated well with the rate of covalent incorporation of 1 mol. of [14C]-I at the active site.
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