A Left-Handed Solution to Peptide Inhibition of the p53–MDM2 Interaction

Authors

  • Min Liu Dr.,

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
    2. The First Affiliated Hospital, Xi'an Jiaotong University School of Medicine (China)
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    • These authors contributed equally to this work.

  • Marzena Pazgier Dr.,

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
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    • These authors contributed equally to this work.

  • Changqing Li Dr.,

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
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    • These authors contributed equally to this work.

  • Weirong Yuan,

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
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  • Chong Li,

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
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  • Wuyuan Lu Prof.

    1. Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., Baltimore, MD 21201 (USA)
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  • This work was supported in part by a Research Scholar Grant CDD112858 from the American Cancer Society and the National Institutes of Health Grants AI072732 and AI061482 (to W.L.). p53=tumor suppressor protein 53; MDM2=murine double minute 2 protein.

Abstract

original image

Throwing tumors a left-hook punch: The oncoprotein MDM2 negatively regulates the activity and stability of the tumor suppressor protein p53, and is an important molecular target for anticancer therapy. Mirror-image phage display identified a high-affinity D-peptide ligand of MDM2 (see structure) that could be developed into a potent and protease-resistant p53 activator with potential antitumor activity.

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