High-Throughput Discovery and Characterization of Covalent Inhibitors for Protein Tyrosine Phosphatases

Zihan Qu; Aaron D Krabill; Zhong-Yin Zhang

doi:10.1007/978-1-0716-3569-8_19

High-Throughput Discovery and Characterization of Covalent Inhibitors for Protein Tyrosine Phosphatases

Methods Mol Biol. 2024:2743:301-316. doi: 10.1007/978-1-0716-3569-8_19.

Authors

Zihan Qu¹, Aaron D Krabill², Zhong-Yin Zhang^{3

4

5

6}

Affiliations

¹ Department of Chemistry, Purdue University, West Lafayette, IN, USA.
² Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
³ Department of Chemistry, Purdue University, West Lafayette, IN, USA. zhang-zy@purdue.edu.
⁴ Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA. zhang-zy@purdue.edu.
⁵ Institute for Cancer Research, Purdue University, West Lafayette, IN, USA. zhang-zy@purdue.edu.
⁶ Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA. zhang-zy@purdue.edu.

PMID: 38147223
DOI: 10.1007/978-1-0716-3569-8_19

Abstract

Covalent inhibition has gained increasing interest in targeting the undruggable protein tyrosine phosphatases (PTPs). However, a systematic method for discovering and characterizing covalent PTP inhibitors has yet to be established. Here, we describe a workflow involving high-throughput screening of covalent fragment libraries and a novel biochemical assay that enables the acquisition of kinetics parameters of PTP inhibition by covalent inhibitors with higher throughput.

Keywords: Covalent inhibition; High-throughput screening; Kinetics of covalent inhibition; Protein tyrosine phosphatase; pNPP assay.

MeSH terms

Biological Assay*
High-Throughput Screening Assays*
Kinetics
Physics
Protein Tyrosine Phosphatases

Substances

Protein Tyrosine Phosphatases