7003-65-8Relevant articles and documents
PROTEIN KINASE C AGONISTS
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Paragraph 0434, (2020/09/12)
The present disclosure relates generally to certain diacylglycerol lactone compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions dis
Do electrostatic interactions with positively charged active site groups tighten the transition state for enzymatic phosphoryl transfer?
Nikolic-Hughes, Ivana,Rees, Douglas C.,Herschlag, Daniel
, p. 11814 - 11819 (2007/10/03)
The effect of electrostatic interactions on the transition-state character for enzymatic phosphoryl transfer has been a subject of much debate. In this work, we investigate the transition state for alkaline phosphatase (AP) using linear free-energy relationships (LFERs). We determined fcat/K M for a series of aryl sulfate ester monoanions to obtain the Bronsted coefficient, βIg, and compared the value to that obtained previously for a series of aryl phosphorothioate ester dianion substrates. Despite the difference in substrate charge, the observed Bronsted coefficients for AP-catalyzed aryl sulfate and aryl phosphorothioate hydrolysis (-0.76 ± 0.14 and -0.77 ± 0.10, respectively) are strikingly similar, with steric effects being responsible for the uncertainties in these values. Aryl sulfates and aryl phosphates react via similar loose transition states in solution. These observations suggest an apparent equivalency of the transition states for phosphorothioate and sulfate hydrolysis reactions at the AP active site and, thus, negligible effects of active site electrostatic interactions on charge distribution in the transition state.
EFFECT OF THE STRUCTURE OF THE LEAVING GROUP, MEDIUM, AND TEMPERATURE ON THE ALKALINE HYDROLYSIS OF PHENYL BENZOATES IN WATER-DIOXANE MIXTURES
Sukhoruchkov, Yu. I.,Polonov, V. M.,Finkel'shtein, B. L.,Istomin, B. I.
, p. 1014 - 1019 (2007/10/02)
A spectrophotometric study was carried out on the kinetics of the alkaline hydrolysis of a series of para-substituted phenyl benzoates PhCO2C6H4X-p in water, 30 and 70 vol. percent aqueous dioxane at 15 deg, 25 deg, and 55 deg C.The bimolecular rate constants depend on the medium composition, temperature, and structure of the leaving group.It is of value to apply linear free energy (LFE) principles in studying these factors, which permits description of the entire set of experimental data by a single multidimensional regression equation.The Arrhenius equation parameters were calculated and this reaction series was shown to be compensated, in contrast to the alkaline hydrolysis of phenyl acetates.The dependence of the ρ constants in the Hammett-Taft equation on the medium composition and temperature indicate that this value is not a linear function of the extent of formation and breakage of bonds in the transition state.
