Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Abstract

A series of systematically modified vanadyl-b-diketone complexes, VO(b-diketone) 2 , bearing substituent groups with different electron inductive properties were synthesized and evaluated as inhibitors against calf-intestine alkaline phosphatase (APase). A combination of biochemical and quantum mechanical techniques were employed to identify structure-activity relationships relevant for rational design of phosphatase inhibitors. Kinetic parameters and activation free energy, enthalpy, and entropy for calf-intestine APase-catalyzed dephosphorylation of para-nitrophenylphosphate were also determined along with the inhibition constants (K i ) for the VO(b-diketone) 2 complexes. Increased positive charge on the vanadyl group increases the inhibition potency of the complex while the absence of an available coordination site on the complex decreases its inhibition potency. These findings correlate well with the results of ab initio electron density calculations for the complexes.

The unique nucleotide specificity of the sucrose synthase from Thermosynechococcus elongatus

“…S 0.5 is defined as the concentration of substrate that produces 50% of the maximal velocity ( V max ) and n H is the Hill coefficient. Alternatively, data were fitted to a random bi–bi mechanism using the program previously reported by Ziegler et al [24]. Kinetic parameters shown were the mean of two independent data sets reproducible within ±10%.…”