Thiophosphate derivatives as inhibitors of tyrosine phosphatases

Thiophosphorylated proteins or peptides are poor substrates of protein phosphatases. As a competitive inhibitor of a protein tyrosine phosphatase, a tyrosine-thiophosphorylated nonapeptide ENDYINASL displays a KI value of 0.25 microM, in comparison with the Km value of 3.1 microM exerted by the enzyme toward the phosphorylated form of the peptide. Furthermore, adenosine 5'-O-3-thiotriphosphate is also an effective competitive inhibitor of the enzyme with a KI value of 1.4 microM. In contrast, ATP and 5'-adenylimidodiphosphate are much less effective, indicating that the thiophosphate group plays a major role in the inhibition process. Further supporting this is the fact that sodium thiophosphate is a more effective inhibitor than inorganic phosphate (IC50 = 0.47 mM versus 15 mM). The inhibition by thiophosphate compounds is specific for PTPs. The data suggest the application of thiophosphate derivatives as specific inhibitors of PTPs.