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Synthesis and Application of Cell-Permeable Metabolites for Modulating Chromatin Modifications Regulated by α-Ketoglutarate-Dependent Enzymes

  • Hunter T. Balduf
  • Antonella Pepe
  • Ann L. KirchmaierEmail author
Protocol
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Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

Direct links between altered metabolism, dysregulation of epigenetic processes, and cancer have been established via investigation of cancer- and syndrome-associated mutations in genes encoding key enzymes of intermediary metabolism. Here, we provide an outline for the synthesis of cell-permeable forms of the cellular metabolites (R)-2-hydroxyglutarate and (L)-2-hydroxyglutarate, and their application for the inhibition of α-ketoglutarate-dependent Jumonji histone demethylases.

Key words

α-ketoglutarate (R)-2-hydroxyglutarate (L)-2-hydroxyglutarate Cancer Leukemia Glioma Epigenetics Histone methylation 

Notes

Acknowledgments

This work was supported by the W.M. Keck Foundation (A.L.K.), Purdue University Center for Cancer Research (http://www.cancerresearch.purdue.edu) Innovative Pilot and Shared Resource Grants (A.L.K.), and a Bird Stair Fellowship (H.B.). This research was also supported by the National Cancer Institute (http://www.cancer.gov) [CCSG CA23168] for data acquired in the Purdue Computational and Medicinal Chemistry Resource.

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Hunter T. Balduf
    • 1
    • 2
  • Antonella Pepe
    • 2
  • Ann L. Kirchmaier
    • 1
    • 2
    Email author
  1. 1.Department of BiochemistryPurdue UniversityWest LafayetteUSA
  2. 2.Purdue Center for Cancer ResearchPurdue UniversityWest LafayetteUSA

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