INHIBITION OF PROTEIN TYROSINE PHOSPHATASES AND SH2 DOMAINS BY A NEUTRAL PHOSPHOTYROSINE MIMETIC

摘要

Methods of inhibiting protein tyrosine phosphatases (PTPs) and Src homology 2 domains (SH2) using neutral phosphotyrosine (pY) mimetics (PTP inhibitors) are provided. Neutral pY mimetics, or PTP inhibitors comprising an aldehyde or mono-ketone substituted aryl group are also provided. Substituents on the aryl groups of the PTP inhibitors provide further affinity for particular PTPs. PTP inhibitors comprising a reactive tripeptide substituent are also provided. Methods of using the neutral, reversible inhibitors as probes for studying the physiological functions of PTPs and SH2 domains are also provided. Methods of treating type II diabetes and obesity by administering a neutral pY mimetic that selectively and reversibly binds with PTP1B are also provided.