Dietrich, Laura, Rathmer, Bernd, Ewan, Kenneth  ORCID: https://orcid.org/0000-0001-6622-9009, Bange, Tanja, Stefan, Heinrichs, Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963, Dennis, Schade and Grossmann, Tom N.
2017.
Cell permeable stapled peptide inhibitor of Wnt signaling that targets β-catenin protein‒protein interactions.
Cell Chemical Biology
24
(8)
, pp. 958-968.
10.1016/j.chembiol.2017.06.013
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Abstract
The Wnt signaling pathway plays a critical role in cell proliferation and differentiation, thus it is often associated with diseases such as cancers. Unfortunately, although attractive, developing anti-cancer strategy targeting Wnt signaling has been challenging given that the most attractive targets are involved in protein-protein interactions (PPIs). Here, we develop a stapled peptide inhibitor that targets the interaction between β-catenin and T cell factor/lymphoid enhancer-binding factor transcription factors, which are crucially involved in Wnt signaling. Our integrative approach combines peptide stapling to optimize proteolytic stability, with lessons learned from cell-penetrating peptide (CPP) design to maximize cellular uptake resulting in NLS-StAx-h, a selective, cell permeable, stapled peptide inhibitor of oncogenic Wnt signaling that efficiently inhibits β-catenin-transcription factor interactions. We expect that this type of integrative strategy that endows stapled peptides with CPP features will be generally useful for developing inhibitors of intracellular PPIs.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences Research Institutes & Centres > European Cancer Stem Cell Research Institute (ECSCRI) |
| Uncontrolled Keywords: | Cell-Penetrating Peptides, New Modalities, Peptidomimetics, Protein-Protein Interaction, Wnt Signaling |
| Publisher: | Elsevier |
| ISSN: | 2451-9456 |
| Date of First Compliant Deposit: | 3 July 2017 |
| Date of Acceptance: | 27 June 2017 |
| Last Modified: | 02 Dec 2024 13:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/102002 |
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