Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer
Abstract Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that conv...
| Автори: | , , , |
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| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Nature Portfolio
2023-05-01
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| Серія: | Nature Communications |
| Онлайн доступ: | https://doi.org/10.1038/s41467-023-38339-2 |
| _version_ | 1826990781234151424 |
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| author | David P. Tilly Jean-Paul Heeb Simon J. Webb Jonathan Clayden |
| author_facet | David P. Tilly Jean-Paul Heeb Simon J. Webb Jonathan Clayden |
| author_sort | David P. Tilly |
| collection | DOAJ |
| description | Abstract Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input – the presence of chloride ions – into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states. The reversible coordination of chloride to a urea binding site triggers a cascade of conformational changes in a chain of ethylene-bridged hydrogen-bonded ureas, switching the chain’s global polarity, that in turn modulates the tautomeric equilibrium of a distal imidazole, and hence its reactivity. Switching reactivities of active sites by dynamically controlling their tautomer states is an untapped strategy for building functional molecular devices with allosteric enzyme-like properties. |
| first_indexed | 2024-04-09T12:48:30Z |
| format | Article |
| id | doaj.art-87f1d19e01b74c12baba99b83d9d6b2e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2025-02-18T08:26:34Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-87f1d19e01b74c12baba99b83d9d6b2e2024-11-03T12:31:10ZengNature PortfolioNature Communications2041-17232023-05-011411710.1038/s41467-023-38339-2Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamerDavid P. Tilly0Jean-Paul Heeb1Simon J. Webb2Jonathan Clayden3School of Chemistry, University of Bristol, Cantock’s CloseSchool of Chemistry, University of Bristol, Cantock’s CloseDepartment of Chemistry, University of ManchesterSchool of Chemistry, University of Bristol, Cantock’s CloseAbstract Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input – the presence of chloride ions – into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states. The reversible coordination of chloride to a urea binding site triggers a cascade of conformational changes in a chain of ethylene-bridged hydrogen-bonded ureas, switching the chain’s global polarity, that in turn modulates the tautomeric equilibrium of a distal imidazole, and hence its reactivity. Switching reactivities of active sites by dynamically controlling their tautomer states is an untapped strategy for building functional molecular devices with allosteric enzyme-like properties.https://doi.org/10.1038/s41467-023-38339-2 |
| spellingShingle | David P. Tilly Jean-Paul Heeb Simon J. Webb Jonathan Clayden Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer Nature Communications |
| title | Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| title_full | Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| title_fullStr | Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| title_full_unstemmed | Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| title_short | Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| title_sort | switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer |
| url | https://doi.org/10.1038/s41467-023-38339-2 |
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