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
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


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 



This work was supported by the W.M. Keck Foundation (A.L.K.), Purdue University Center for Cancer Research ( 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 ( [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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