@article{16c57130a3a84573b17e890225d0e1ae,
title = "On the evaluation of a small molecule mimic of chymotrypsin",
abstract = "An alternative analysis of a recently published serine protease model suggests a more benign role for its imidazole-carboxylate moiety.",
author = "Zimmerman, {Steven C.}",
note = "Funding Information: It is not clear why the imidazole-benzoate group of 1 slows down the rate of hydrolysis relative to p-cyclodextrin. A change in conformation of the hydrophobic pocket or an interaction between the substrate and the imidazolebenzoate group may result in a less favorable positioning of the carbonyl group for nucleophilic attack by the secondary hydroxyl group. It is remarkable how difficult it has been to observe 0-acylation catalyzed by an internal imidazole. Hydroxy-imidazoles reported to date undergo preferential N-acylation,b catalyze the attack of a water molecule,7 or have undetermined mechanisms. Brown{\textquoteright}s recently reported system appears to be the only documented model of the acylation mechanism proposed to operate in the chymotrypsin active site.8 In conclusion, the experimental data reported for the hydrolysis of m-(fert-butyl)phenyl acetate catalyzed by 1 is most consistent with a mechanism involving nucleophilic attack by an ionized secondary hydroxyl on the substrate carbonyl without involvement of the imidazolecarboxylate moiety. Thus, an effective mimic for the chymotrypsin catalytic cycle remains elusive although substantial progress has been reported toward this goal.9,10 Acknowledgement: This work was funded by the National Institutes of Health (GM39782). Stimulating discussions with Prof. Jik Chin are gratefully acknowledged.",
year = "1989",
month = jan,
day = "1",
doi = "10.1016/S0040-4039(00)99359-6",
language = "English",
volume = "30",
pages = "4357--4358",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Ltd.",
number = "33",
}