Petrenas, R., Hawkins, O.A., Jones, J.F. orcid.org/0009-0004-6876-9243 et al. (8 more authors) (2025) Confinement and catalysis within de novo designed peptide barrels. Journal of the American Chemical Society, 147 (4). pp. 3796-3803. ISSN 0002-7863
Abstract
De novo protein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities. To address this, here we describe the design, characterization, and application of small-molecule:peptide ternary complexes in aqueous solution. This uses α-helical barrel (αHB) peptide assemblies, which comprise 5 or more α helices arranged around central channels. These channels are solvent accessible, and their internal dimensions and chemistries can be altered predictably. Thus, αHBs are analogous to "molecular flasks" made in supramolecular, polymer, and materials chemistry. Using Förster resonance energy transfer as a readout, we demonstrate that specific αHBs can accept two different organic dyes, 1,6-diphenyl-1,3,5-hexatriene and Nile red, in close proximity. In addition, two anthracene molecules can be accommodated within an αHB to promote anthracene photodimerization. However, not all ternary complexes are productive, either in energy transfer or photodimerization, illustrating the control that can be exerted by judicious choice and design of the αHB.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0. (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Aromatic compounds; Fluorescence; Fluorescence resonance; energy transfer; Hydrocarbons; Peptides and proteins |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences |
Funding Information: | Funder Grant number Engineering and Physical Sciences Research Council EP/T012455/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2025 10:04 |
Last Modified: | 31 Jan 2025 10:04 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/jacs.4c16633 |
Related URLs: | |
Sustainable Development Goals: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222551 |
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Licence: CC-BY 4.0