STUDIES OF TRANSITION-STATE STRUCTURES IN PHOSPHORYL TRANSFER-REACTIONS OF PHOSPHODIESTERS OF P-NITROPHENOL

被引：71

作者：

HENGGE, AC ^{[1
]}

TOBIN, AE ^{[1
]}

CLELAND, WW ^{[1
]}

机构：

[1] UNIV WISCONSIN,INST ENZYME RES,MADISON,WI 53705

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 1995年 / 117卷 / 22期

关键词：

D O I：

10.1021/ja00127a003

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Heavy-atom kinetic isotope effects have been used to study the transition states for a number of phosphoryl transfer reactions of the phosphodiesters p-tert-butylphenyl p-nitrophenyl phosphate (1) and 3,3-dimethylbutyl p-nitrophenyl phosphate (2). The alkaline and acid hydrolysis reactions and the reaction with phosphodiesterase I from snake venom were studied with each substrate. In addition, the hydrolysis reactions of 1 catalyzed by bis-(imidazolyl)- and by mono(imidazolyl)-beta-cyclodextrins were studied. The isotope effects measured were the primary O-18 isotope effect in the p-nitrophenyl leaving group, the secondary O-18 isotope effect in the nonbridge oxygen atoms, and the N-15 isotope effect in the leaving group. The data indicate similar early transition-state structures for the aqueous hydrolysis reactions of the two compounds with little bond cleavage to the leaving group. In contrast, significant differences in transition-state structure between the substrates are seen in their reactions with phosphodiesterase I. Compound 1 is a substrate for the imidazolyl-beta-cyclodextrin catalysts, which operate as simple general base catalysts for this substrate. Transition-state bond cleavage to the leaving group is much further advanced in these reactions than in the uncatalyzed aqueous reactions.

引用

页码：5919 / 5926

页数：8

共 33 条

[21]

Kirby A.J., Younas M., J. Chem. Soc. B, pp. 510-513, (1970)

[22]

Knight W.B., Weiss P.M., Cleland W.W., J. Am. Chem. Soc., 108, pp. 2759-2761, (1986)

[23]

Hengge A.C., Hess R.A., J. Am. Chem. Soc., 116, pp. 11256-11263, (1994)

[24]

Bourne N., Williams A., J. Org. Chem., 49, pp. 1200-1204, (1984)

[25]

Deacon T., Farrar C.R., Sikkel B.J., Williams A., J. Am. Chem. Soc., 110, (1978)

[26]

Culp J.S., Butler L.G., Arch. Biochem. Biophys., 246, pp. 245-249, (1986)

[27]

Pollack S.E., Uchida T., Auld D.S., J. Protein Chem., 2, pp. 1-11, (1983)

[28]

Guthrie P.J., J. Am. Chem. Soc., 99, pp. 3991-4001, (1977)

[29]

Kluger R., Covitz F., Dennis E., Williams L.D., Westheimer F.H., J. Am. Chem. Soc., 91, pp. 6066-6072, (1969)

[30]

Anslyn E.V., personal communication: manuscript in preparation

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