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.
Zhao
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Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
D000595:Amino Acid Sequence; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D063086:Organothiophosphates / Q000737:chemistry; D010748:Phosphopeptides / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D009842:Oligopeptides; D063086:Organothiophosphates; D010748:Phosphopeptides; D017027:Protein Tyrosine Phosphatases