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

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Epigenetics and Gene Expression in Cancer, Inflammatory and Immune Diseases

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

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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.

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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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Authors and Affiliations

  1. Department of Biochemistry, Purdue University, 175 S. University Street, West Lafayette, IN, 47907, USA

    Hunter T. Balduf & Ann L. Kirchmaier

  2. Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA

    Hunter T. Balduf, Antonella Pepe & Ann L. Kirchmaier

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  1. Hunter T. Balduf
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  2. Antonella Pepe
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  3. Ann L. Kirchmaier
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Correspondence to Ann L. Kirchmaier .

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Editors and Affiliations

  1. Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA

    Barbara Stefanska

  2. Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine University of Liverpool, Liverpool, United Kingdom

    David J. MacEwan

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Balduf, H.T., Pepe, A., Kirchmaier, A.L. (2017). Synthesis and Application of Cell-Permeable Metabolites for Modulating Chromatin Modifications Regulated by α-Ketoglutarate-Dependent Enzymes. In: Stefanska, B., MacEwan, D. (eds) Epigenetics and Gene Expression in Cancer, Inflammatory and Immune Diseases. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6743-8_5

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  • DOI: https://doi.org/10.1007/978-1-4939-6743-8_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6741-4

  • Online ISBN: 978-1-4939-6743-8

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