Articles | Volume 2, issue 1
Research article
02 Jun 2021
Research article |  | 02 Jun 2021

Small-molecule inhibitors of the PDZ domain of Dishevelled proteins interrupt Wnt signalling

Nestor Kamdem, Yvette Roske, Dmytro Kovalskyy, Maxim O. Platonov, Oleksii Balinskyi, Annika Kreuchwig, Jörn Saupe, Liang Fang, Anne Diehl, Peter Schmieder, Gerd Krause, Jörg Rademann, Udo Heinemann, Walter Birchmeier, and Hartmut Oschkinat

Related subject area

Field: Liquid-state NMR | Topic: Applications – biological macromolecules
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Cited articles

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Short summary
The Wnt signalling pathway plays a major role in prevention of cancer, whereby the protein Dishevelled connects from the transmembrane receptor Frizzled to downstream effectors via its PDZ domain. Here, cycles of chemical synthesis and structural biology are applied to develop PDZ ligands that block the Frizzled–Dishevelled interaction using NMR for screening, in ligand development, and for deriving structure–activity relationships. Cellular reporter assays demonstrate their efficacy.