Design and Synthesis of Class-Selective Activity Probes for Protein Tyrosine Phosphatases

Abstract

Two mechanism-based activity probes, adopting a cassette-like design, for protein tyrosine phosphatases (PTPs) were synthesized. Both probes carry a phosphate group that serves as the recognition head for the target PTPs but differ in their reporter groups; probe LCL-1 uses a dansyl fluorophore, while LCL-2 has a biotin reporter group. LCL-1 and LCL-2 are specifically activated by phosphatase, leading to its covalent labeling, as exemplified with PTP-1B. However, they show no activation with other classes of hydrolases, including trypsin and β-galactosidase. LCL-1 and LCL-2 thus represent the first example of class-selective probes for phosphatases. Keywords: activity probe • labeling • protein tyrosine phosphatase • PTP1B • proteomics • quinone methide • signaling