Modulators of 14-3-3 Protein-Protein Interactions

Loes M. Stevers, Eline Sijbesma, Maurizio Botta, Carol MacKintosh, Tomas Obsil, Isabelle Landrieu, Ylenia Cau, Andrew J. Wilson, Anna Karawajczyk, Jan Eickhoff, Jeremy Davis, Michael Hann, Gavin O'Mahony, Richard G. Doveston, Luc Brunsveld, Christian Ottmann (Lead / Corresponding author)

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    188 Citations (Scopus)
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    Abstract

    Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein-protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as "undruggable" targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products.

    Original languageEnglish
    Pages (from-to)3755-3778
    Number of pages24
    JournalJournal of Medicinal Chemistry
    Volume61
    Issue number9
    Early online date2 Oct 2017
    DOIs
    Publication statusPublished - 10 May 2018

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