Tumor metastasis is responsible for approximately 90% of cancer related deaths. As a consequence, there is a critical need for the development of probes capable of quantifying the metastatic potential of tumors. Current research demonstrates that the enzymatic activity of protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-, and threonine-rich sequence (PEST) is essential for productive cell migration. Indeed, dysregulation of PTP-PEST enzymatic activity is potentially linked to the development of a metastatic phenotype. However, there is a lack of assays available for quantifying endogenous PTP-PEST activity from cell lysates. Herein, we describe the development and validation of a chemosensor for PTP-PEST. This probe relies on the phosphorylation-sensitive amino acid known as Sox in order to provide a direct, real-time readout of PTP-PEST activity.  Utilizing this approach we have synthesized a sensitive PTP-PEST activity probe with a limit of detection of 0.5 nM.  This chemosensor is also selective for PTP-PEST among a panel of other PTPs, and can be used to detect PTP-PEST activity in unfractionated cell lysates. In the long term, this probe could be used to profile PTP-PEST activity in tumor cell lines with varying metastatic potential as well as develop tool compounds for inhibition of this important enzyme.<br/>

Development of a direct activity probe for a critical regulator of metastatic signaling

253rd National Meeting (2017)

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