Kinetics and molecular modelling studies of the inhibition of protein tyrosine phosphatases by N,N-dimethylhydroxylamine complexes of vanadium(V)

 Bis(N,N-dimethylhydroxamido)hydroxooxovanadate and a derivative complex formed with dithiothreitol have been shown to be excellent inhibitors of the function of two protein tyrosine phosphatases, leucocyte antigen related phosphatase (LAR) and protein tyrosine phosphatase-1B (PTP1B). Inhibition constants of 1.0±0.3 μM and 2.3±0.3 μM, respectively, were determined for the inhibition of LAR by the two complexes. The inhibition of PTP1B is not substantially different. Unlike the structurally related hydrogen peroxide complexes of vanadium, these complexes inhibit in a fully reversible manner that is consistent with a non-oxidative process. Molecular modelling studies suggest the main stabilizing interaction is a cyclic H-bonded structure involving the conserved active site aspartate. Hydrophobic stabilization interactions were also suggested. Received: 17 February 1998 / Accepted: 6 July 1998