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Hyperpolarized Binding Pocket Nuclear Overhauser Effect for Determination of Competitive Ligand Binding

Authors

  • Youngbok Lee,

    1. Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, TX 77843 (USA)
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    • These authors contributed equally to this work.

  • Haifeng Zeng,

    1. Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, TX 77843 (USA)
    2. Current address: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205 (USA)
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    • These authors contributed equally to this work.

  • Dr. Adam Mazur,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
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  • Melanie Wegstroth,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
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  • Priv.-Doz. Dr. Teresa Carlomagno,

    1. EMBL Heidelberg, Meyerhofstr. 1, 69117 Heidelberg (Germany)
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  • Dr. Marcel Reese,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
    2. Current address: Department of Chemistry and Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • Dr. Donghan Lee,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
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  • Dr. Stefan Becker,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
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  • Prof. Dr. Christian Griesinger,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany)
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  • Prof. Dr. Christian Hilty

    Corresponding author
    1. Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, TX 77843 (USA)
    • Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, TX 77843 (USA)
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  • C.H. thanks the Camille and Henry Dreyfus Foundation for a New Faculty Award. Support from the National Science Foundation (grant number CHE-0846402), and from the Texas A&M University startup funds is gratefully acknowledged. C.G. thanks the Max Planck Society for support. This project was also performed under the auspices of the BMBF project (“Neue Verfahren der Bio-NMR zur Optimierung und Beschleunigung strukturbasierter Wirkstoffentwicklung”) and the EU funded FP7-Bio-NMR project (project number: 261863).

Abstract

original image

Protein-mediated polarization transfer: Ligands L1 and L2 that competitively bind to a protein are subject to indirect spin-polarization transfer through the binding site of the protein. If protons HL1 of one ligand are hyperpolarized by dynamic nuclear polarization (DNP, see picture), signal intensities in the NMR spectrum of the second ligand become enhanced. The relative build-up of signal of the second ligand yields information on its binding epitope.

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