A combinatorial strategy for the acquisition of potent and specific protein tyrosine phosphatase inhibitors

Sheng Zhang, Lan Chen, David S. Lawrence, Zhong Yin Zhang

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, regulate many cellular processes, such as proliferation, differentiation, migration, apoptosis, and immune responses. Small molecule inhibitors against PTPs are valuable both as powerful tools to study the functions of target PTPs and as lead compounds for pharmacological development. Here, we describe a novel combinatorial library approach to target simultaneously both the active site pocket and a peripheral secondary binding site for the acquisition of potent and specific PTP inhibitors. Fluorescence tagging during combinatorial library synthesis enables fluorescence polarization-based high-throughput screening of the resulting library, leading to identification of a TC-PTP inhibitor.

Original languageEnglish (US)
Title of host publicationRational Drug Design
Subtitle of host publicationMethods and Protocols
EditorsYi Zheng
Pages53-65
Number of pages13
DOIs
StatePublished - Nov 12 2012

Publication series

NameMethods in Molecular Biology
Volume928
ISSN (Print)1064-3745

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Keywords

  • Combinatorial chemistry
  • Fluorescence polarization
  • Fluorescence tagged
  • High-throughput screening
  • Peripheral binding site
  • Protein tyrosine phosphatases (PTPs)
  • PTP inhibitor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Zhang, S., Chen, L., Lawrence, D. S., & Zhang, Z. Y. (2012). A combinatorial strategy for the acquisition of potent and specific protein tyrosine phosphatase inhibitors. In Y. Zheng (Ed.), Rational Drug Design: Methods and Protocols (pp. 53-65). (Methods in Molecular Biology; Vol. 928). https://doi.org/10.1007/978-1-62703-008-3-5