Quiescent affinity inactivators of protein tyrosine phosphatases.
alpha-Halobenzylphosphonates were investigated as possible inactivators of protein tyrosine phosphatases (PTPases). These compounds inactivate the Yersinia PTPase (Yop51*delta 162) in a time- and concentration-dependent fashion. This inactivation is active-site directed and irreversible, and is surprisingly rapid in light of the stability of the alpha-halobenzylphosphonates toward nucleophiles in solution. The potential of these molecules for probing the stereochemistry of PTPase inactivation, as well as for providing a useful paradigm for the design of more potent PTPase inhibitors is discussed.
Department of Chemistry, Indiana University, Bloomington 47405, USA.
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Taylor
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Zhang
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Widlanski
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D014462:Ultrafiltration; D015008:Yersinia enterocolitica / Q000737:chemistry*
D004791:Enzyme Inhibitors; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D017027:Protein Tyrosine Phosphatases