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Issue 7, 2017
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Covalent inhibition of protein tyrosine phosphatases

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Protein tyrosine phosphatases (PTPs) are a large family of 107 signaling enzymes that catalyze the hydrolytic removal of phosphate groups from tyrosine residues in a target protein. The phosphorylation status of tyrosine residues on proteins serve as a ubiquitous mechanism for cellular signal transduction. Aberrant function of PTPs can lead to many human diseases, such as diabetes, obesity, cancer, and autoimmune diseases. As the number of disease relevant PTPs increases, there is urgency in developing highly potent inhibitors that are selective towards specific PTPs. Most current efforts have been devoted to the development of active site-directed and reversible inhibitors for PTPs. This review summarizes recent progress made in the field of covalent inhibitors to target PTPs. Here, we discuss the in vivo and in vitro inactivation of various PTPs by small molecule-containing electrophiles, such as Michael acceptors, α-halo ketones, epoxides, and isothiocyanates, etc. as well as oxidizing agents. We also suggest potential strategies to transform these electrophiles into isozyme selective covalent PTP inhibitors.

Graphical abstract: Covalent inhibition of protein tyrosine phosphatases

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Publication details

The article was received on 13 Mar 2017, accepted on 09 May 2017 and first published on 10 May 2017

Article type: Review Article
DOI: 10.1039/C7MB00151G
Citation: Mol. BioSyst., 2017,13, 1257-1279
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    Covalent inhibition of protein tyrosine phosphatases

    K. V. Ruddraraju and Z. Zhang, Mol. BioSyst., 2017, 13, 1257
    DOI: 10.1039/C7MB00151G

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