Inhibition of acid, alkaline, and tyrosine (PTP1B) phosphatases by novel vanadium complexes

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• 作者：Craig C. McLauchlan ; Jaqueline D. Hooker ; Marjorie A. Jones ; Zaneta Dymon ; Emily A. Backhus ; Bradley A. Greiner ; Nicole A. Dorner ; Mary A. Youkhana ; Lisa M. Manus
• 关键词：Vanadium ; Phosphatase inhibition ; Vanadium complexes ; X-ray crystallography
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：104
• 期：3
• 页码：274-281
• 全文大小：291 K

文摘

In the course of our investigations of vanadium-containing complexes for use as insulin-enhancing agents, we have generated a series of novel vanadium coordination complexes with bidentate ligands. Specifically we have focused on two ligands: anthranilate (anc⁻), a natural metabolite of tryptophan, and imidizole-4-carboxylate (imc⁻), meant to mimic naturally occurring N-donor ligands. For each ligand, we have generated a series of complexes containing the V(III), V(IV), and V(V) oxidation states. Each complex was investigated using phosphatase inhibition studies of three different phosphatases (acid, alkaline, and tyrosine (PTP1B) phosphatase) as prima facia evidence for potential use as an insulin-enhancing agent. Using p-nitrophenyl phosphate as an artificial phosphatase substrate, the levels of inhibition were determined by measuring the absorbance of the product at 405 nm using UV/vis spectroscopy. Under our experimental conditions, for instance, V(imc)₃ appears to be as potent an inhibitor of alkaline phosphatase as sodium orthovanadate when comparing the K_cat/K_m term. VO(anc)₂ is as potent an inhibitor of acid phosphatase and tyrosine phosphatase as the Na₃VO₄. Thus, use of these complexes can increase our mechanistic understanding of the effects of vanadium in vivo.