These authors contributed equally to this work.
Immunosuppressive Small Molecule Discovered by Structure-Based Virtual Screening for Inhibitors of Protein–Protein Interactions†
Article first published online: 16 NOV 2011
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 51, Issue 1, pages 258–261, January 2, 2012
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
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.).
- Issue published online: 29 DEC 2011
- Article first published online: 16 NOV 2011
- Manuscript Received: 20 AUG 2011
- Swiss National Science Foundation. Grant Number: 205321-134783
- OPO-Foundation Zurich
- Deutsche Forschungsgemeinschaft. Grant Number: WA 2873/1-1
- drug design;
- protein–protein interactions;
- virtual screening
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.