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.