Articles | Volume 2, issue 1
https://doi.org/10.5194/mr-2-355-2021
https://doi.org/10.5194/mr-2-355-2021
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

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Interactive discussion

Status: closed

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • CC1: 'Comment on mr-2021-20', Jie Zheng, 03 Mar 2021
    • AC1: 'Reply on CC1', Hartmut Oschkinat, 14 Apr 2021
    • AC3: 'Reply on CC1', Hartmut Oschkinat, 14 Apr 2021
  • RC1: 'Comment on mr-2021-20', Mingjie Zhang, 11 Mar 2021
    • AC2: 'Reply on RC1', Hartmut Oschkinat, 14 Apr 2021
  • RC2: 'Comment on mr-2021-20', Anonymous Referee #2, 15 Mar 2021
    • AC4: 'Reply on RC2', Hartmut Oschkinat, 14 Apr 2021

Peer review completion

AR: Author's response | RR: Referee report | ED: Editor decision
AR by Hartmut Oschkinat on behalf of the Authors (27 Apr 2021)  Author's response    Author's tracked changes    Manuscript
ED: Publish subject to corrections (28 Apr 2021) by Rolf Boelens
AR by Hartmut Oschkinat on behalf of the Authors (30 Apr 2021)  Author's response    Manuscript

Post-review adjustments

AA: Author's adjustment | EA: Editor approval
AA by Hartmut Oschkinat on behalf of the Authors (28 May 2021)   Author's adjustment  
EA: Adjustments approved (28 May 2021) by Rolf Boelens
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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.