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Research Article

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

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Pages 22-28 | Received 17 Sep 2007, Accepted 31 Oct 2007, Published online: 20 Oct 2008
 

Abstract

A series of systematically modified vanadyl-β-diketone complexes, VO(β-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 (Ki) for the VO(β-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.

Acknowledgements

This research was supported by Loyola University Chicago through a Faculty Research Support Grant (AWH) and New Faculty Research Support Grant (MAB). Research Corporation provided support through a Research Innovation Award (JF).

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