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Differential sensing with arrays of de novo designed peptide assemblies

Author

Listed:
  • William M. Dawson

    (University of Bristol, Cantock’s Close)

  • Kathryn L. Shelley

    (University of Bristol, Cantock’s Close
    University of Bristol, Medical Sciences Building, University Walk)

  • Jordan M. Fletcher

    (University of Bristol, Cantock’s Close
    Rosa Biotech, Science Creates St Philips)

  • D. Arne Scott

    (University of Bristol, Cantock’s Close
    University of Bristol, Medical Sciences Building, University Walk
    Rosa Biotech, Science Creates St Philips)

  • Lucia Lombardi

    (University of Bristol, Cantock’s Close
    University of Bristol, School of Chemistry
    Imperial College London)

  • Guto G. Rhys

    (University of Bristol, Cantock’s Close
    University of Bayreuth
    Cardiff University, Main Building)

  • Tania J. LaGambina

    (Rosa Biotech, Science Creates St Philips)

  • Ulrike Obst

    (Rosa Biotech, Science Creates St Philips)

  • Antony J. Burton

    (University of Bristol, Cantock’s Close
    AstraZeneca)

  • Jessica A. Cross

    (University of Bristol, Cantock’s Close
    University of Bristol, Medical Sciences Building, University Walk)

  • George Davies

    (University of Bristol, Cantock’s Close)

  • Freddie J. O. Martin

    (University of Bristol, Cantock’s Close)

  • Francis J. Wiseman

    (University of Bristol, Cantock’s Close)

  • R. Leo Brady

    (University of Bristol, Medical Sciences Building, University Walk)

  • David Tew

    (GlaxoSmithKline (GSK))

  • Christopher W. Wood

    (University of Bristol, Cantock’s Close
    University of Bristol, Medical Sciences Building, University Walk
    University of Edinburgh)

  • Derek N. Woolfson

    (University of Bristol, Cantock’s Close
    University of Bristol, Medical Sciences Building, University Walk
    University of Bristol, School of Chemistry)

Abstract

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings.

Suggested Citation

  • William M. Dawson & Kathryn L. Shelley & Jordan M. Fletcher & D. Arne Scott & Lucia Lombardi & Guto G. Rhys & Tania J. LaGambina & Ulrike Obst & Antony J. Burton & Jessica A. Cross & George Davies & F, 2023. "Differential sensing with arrays of de novo designed peptide assemblies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36024-y
    DOI: 10.1038/s41467-023-36024-y
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    References listed on IDEAS

    as
    1. Guto G. Rhys & Christopher W. Wood & Eric J. M. Lang & Adrian J. Mulholland & R. Leo Brady & Andrew R. Thomson & Derek N. Woolfson, 2018. "Maintaining and breaking symmetry in homomeric coiled-coil assemblies," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Alfredo Quijano-Rubio & Hsien-Wei Yeh & Jooyoung Park & Hansol Lee & Robert A. Langan & Scott E. Boyken & Marc J. Lajoie & Longxing Cao & Cameron M. Chow & Marcos C. Miranda & Jimin Wi & Hyo Jeong Hon, 2021. "De novo design of modular and tunable protein biosensors," Nature, Nature, vol. 591(7850), pages 482-487, March.
    3. Ole Herud-Sikimić & Andre C. Stiel & Martina Kolb & Sooruban Shanmugaratnam & Kenneth W. Berendzen & Christian Feldhaus & Birte Höcker & Gerd Jürgens, 2021. "A biosensor for the direct visualization of auxin," Nature, Nature, vol. 592(7856), pages 768-772, April.
    Full references (including those not matched with items on IDEAS)

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