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 phosph atase, a tyrosine-thiophosphorylated nonapeptide ENDYINASL displays a K-I value of 0.25 mu M, in comparison with the K-m value of 3.1 mu M e xerted by the enzyme toward the phosphorylated form of the peptide. Fu rthermore, adenosine 5'-O-3-thiotriphosphate is also an effective comp etitive inhibitor of the enzyme with a K-I value of 1.4 mu M. In contr ast, ATP and 5'-adenyl imidodiphosphate are much less effective, indic ating that the thiophosphate group plays a major role in the inhibitio n process. Further supporting this is the fact that sodium thiophospha te is a more effective inhibitor than inorganic phosphate (IC50 = 0.47 mM versus 15 mM). The inhibition by thiophosphate compounds is specif ic for PTPs. The data suggest the application of thiophosphate derivat ives as specific inhibitors of PTPs. (C) 1996 Academic Press. Inc.