Differential sensing with arrays of de novo designed peptide assemblies

Dawson, William M., Shelley, Kathryn L., Fletcher, Jordan M., Scott, D. Arne, Lombardi, Lucia, Rhys, Guto G., LaGambina, Tania J., Obst, Ulrike, Burton, Antony J., Cross, Jessica A., Davies, George, Martin, Freddie J. O., Wiseman, Francis J., Brady, R. Leo, Tew, David, Wood, Christopher W. and Woolfson, Derek N. 2023. Differential sensing with arrays of de novo designed peptide assemblies. Nature Communications 14 , 383. 10.1038/s41467-023-36024-y

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	25 January 2023
Date of Acceptance:	11 January 2023
Last Modified:	11 Oct 2023 18:39
URI:	https://orca.cardiff.ac.uk/id/eprint/156237

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