Communication

Immunosuppressive Small Molecule Discovered by Structure-Based Virtual Screening for Inhibitors of Protein–Protein Interactions†

  1. Tim Geppert1,
  2. Stefanie Bauer2,
  3. Dr. Jan A. Hiss1,
  4. Elea Conrad2,
  5. Michael Reutlinger1,
  6. Dr. Petra Schneider1,
  7. Dr. Martin Weisel3,
  8. Bernhard Pfeiffer1,
  9. Prof. Dr. Karl-Heinz Altmann1,
  10. Priv.-Doz. Dr. Zoe Waibler2,‡,
  11. Prof. Dr. Gisbert Schneider1,‡,*

Article first published online: 16 NOV 2011

DOI: 10.1002/anie.201105901

Issue

Angewandte Chemie International Edition

Angewandte Chemie International Edition

Volume 51, Issue 1, pages 258–261, January 2, 2012

Additional Information

How to Cite

Geppert, T., Bauer, S., Hiss, J. A., Conrad, E., Reutlinger, M., Schneider, P., Weisel, M., Pfeiffer, B., Altmann, K.-H., Waibler, Z. and Schneider, G. (2012), Immunosuppressive Small Molecule Discovered by Structure-Based Virtual Screening for Inhibitors of Protein–Protein Interactions. Angew. Chem. Int. Ed., 51: 258–261. doi: 10.1002/anie.201105901

Author Information

  1. 1

    Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)

  2. 2

    Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)

  3. 3

    Goethe-Universität Frankfurt, Institut für Organische Chemie und Chemische Biologie, Beilstein-Stiftungsprofessur, Frankfurt (Germany)

  1. ‡

    These authors contributed equally to this work.

*Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)

  1. †

    We thank Kay-Martin Hanschmann and Peter Volkers for statistical analyses, and Gerd Sutter for providing MVA. Martin Löwer implemented the VirtualLigand software. The Chemical Computing Group Inc. kindly provided a research license for MOE. This research was supported by the Swiss National Science Foundation (grant 205321-134783), the OPO-Foundation Zurich (G.S.), and the Deutsche Forschungsgemeinschaft (grant WA 2873/1-1 to Z.W.).

  2. ‡

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 29 DEC 2011
  2. Article first published online: 16 NOV 2011
  3. Manuscript Received: 20 AUG 2011

Funded by

  • Swiss National Science Foundation. Grant Number: 205321-134783
  • OPO-Foundation Zurich
  • Deutsche Forschungsgemeinschaft. Grant Number: WA 2873/1-1

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Keywords:

  • bioinformatics;
  • drug design;
  • interferon;
  • protein–protein interactions;
  • virtual screening
Thumbnail image of graphical abstract

Interfering with interferon: A low-molecular-weight inhibitor has been discovered that blocks the interaction between interferon-α (IFN-α) and its receptor (see picture for a model of the interfaces). The resulting lead compound significantly reduces IFN-α production in vitro. NMR and SPR experiments confirm the direct interaction of the inhibitor with IFN-α.

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