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Helix-mediated protein–protein interactions as targets for intervention using foldamers

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Abstract

Protein–protein interactions (PPIs) play a central role in virtually all biological processes and have been the focus of intense investigation from structural molecular biology to cell biology for the majority of the last two decades and, more recently, are emerging as important targets for pharmaceutical intervention. A common motif found at the interface of PPIs is the α-helix, suggesting that, in the same way as the “lock and key” model has evolved for competitive inhibition of enzymes, it should be possible to elaborate “rule-based” approaches for inhibition of helix-mediated PPIs. This review will describe the biological function and structural features of a series of representative helix-mediated PPIs and discuss approaches that are being developed to target these interactions with small molecules that employ non-natural amino acids.

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Acknowledgments

The authors would like to acknowledge the financial support of the European Research Council [ERC-StG-240324].

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The authors declare that they have no conflict of interest.

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  1. Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK

    Thomas A. Edwards & Andrew J. Wilson

  2. School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK

    Andrew J. Wilson

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  1. Thomas A. Edwards
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Correspondence to Andrew J. Wilson.

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Edwards, T.A., Wilson, A.J. Helix-mediated protein–protein interactions as targets for intervention using foldamers. Amino Acids 41, 743–754 (2011). https://doi.org/10.1007/s00726-011-0880-8

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