Immunosuppressive Small Molecule Discovered by Structure-Based Virtual Screening for Inhibitors of Protein–Protein Interactions†
Tim Geppert
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorStefanie Bauer
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
Search for more papers by this authorDr. Jan A. Hiss
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorElea Conrad
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
Search for more papers by this authorMichael Reutlinger
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorDr. Petra Schneider
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorDr. Martin Weisel
Goethe-Universität Frankfurt, Institut für Organische Chemie und Chemische Biologie, Beilstein-Stiftungsprofessur, Frankfurt (Germany)
Search for more papers by this authorBernhard Pfeiffer
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorProf. Dr. Karl-Heinz Altmann
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorPriv.-Doz. Dr. Zoe Waibler
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Prof. Dr. Gisbert Schneider
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
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)Search for more papers by this authorTim Geppert
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorStefanie Bauer
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
Search for more papers by this authorDr. Jan A. Hiss
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorElea Conrad
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
Search for more papers by this authorMichael Reutlinger
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorDr. Petra Schneider
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorDr. Martin Weisel
Goethe-Universität Frankfurt, Institut für Organische Chemie und Chemische Biologie, Beilstein-Stiftungsprofessur, Frankfurt (Germany)
Search for more papers by this authorBernhard Pfeiffer
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorProf. Dr. Karl-Heinz Altmann
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
Search for more papers by this authorPriv.-Doz. Dr. Zoe Waibler
Junior Research Group “Novel Vaccination Strategies and Early Immune Responses”, Paul-Ehrlich-Institut, 63225 Langen (Germany)
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Prof. Dr. Gisbert Schneider
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich (Switzerland)
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)Search for more papers by this authorWe 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.).
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.
Supporting Information
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