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Updated: May 12, 2026
09:16
Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
Selective detection of allosteric phosphatase inhibitors
Ralf Schneider1, Claudia Beumer, Jeffrey R Simard
1Chemical Genomics Centre der Max-Planck-Gesellschaft, Dortmund, Germany.
Journal of the American Chemical Society
|April 25, 2013
Summary
Developing novel phosphatase inhibitors is crucial for treating diseases like cancer. This study introduces a new high-throughput screening assay to discover allosteric phosphatase inhibitors, overcoming limitations of previous methods.
Area of Science:
- Biochemistry
- Enzymology
- Drug Discovery
Background:
- Protein phosphorylation by kinases and phosphatases regulates cellular functions.
- Dysregulation of phosphorylation contributes to diseases like cancer and inflammation.
- While kinase inhibitors are successful, no phosphatase inhibitors are clinically approved due to issues with selectivity and charge.
Purpose of the Study:
- To develop a novel assay for discovering allosteric phosphatase inhibitors.
- To address the lack of suitable screening systems for allosteric modulators.
- To enable the identification of drug candidates with improved pharmacological properties.
Main Methods:
- Development of a novel binding assay.
- Assay designed to detect ligands binding to an allosteric pocket.
- Assay validated for high-throughput screening (HTS).
Main Results:
- The assay successfully detects ligands binding to the allosteric pocket of protein tyrosine phosphatase 1B (PTP1B).
- The assay demonstrates clear discrimination between allosteric and substrate-competitive ligands.
- The assay is suitable for high-throughput screening applications.
Conclusions:
- A novel, selective assay for allosteric phosphatase inhibitor discovery has been developed.
- This assay facilitates the identification of novel phosphatase modulators.
- The assay overcomes limitations of previous methods, paving the way for new therapeutics.
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