Inhibition of acid, alkaline, and tyrosine (PTP1B) phosphatases by novel vanadium complexes.
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 405nm 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 Na(3)VO(4). Thus, use of these complexes can increase our mechanistic understanding of the effects of vanadium in vivo.
McLauchlan
Craig C
CC
Illinois State University, Department of Chemistry, Campus Box 4160, Normal, IL 61790-4160, United States. McLauchlan@IllinoisState.edu
Hooker
Jaqueline D
JD
Jones
Marjorie A
MA
Dymon
Zaneta
Z
Backhus
Emily A
EA
Greiner
Bradley A
BA
Dorner
Nicole A
NA
Youkhana
Mary A
MA
Manus
Lisa M
LM
D018360:Crystallography, X-Ray; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014639:Vanadium / Q000737:chemistry*
D007328:Insulin; D007527:Isoenzymes; D008024:Ligands; D014639:Vanadium; D010744:Phosphoric Monoester Hydrolases