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Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer

Author

Listed:
  • David P. Tilly

    (University of Bristol, Cantock’s Close
    University of Manchester)

  • Jean-Paul Heeb

    (University of Bristol, Cantock’s Close)

  • Simon J. Webb

    (University of Manchester)

  • Jonathan Clayden

    (University of Bristol, Cantock’s Close)

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.

Suggested Citation

  • David P. Tilly & Jean-Paul Heeb & Simon J. Webb & Jonathan Clayden, 2023. "Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38339-2
    DOI: 10.1038/s41467-023-38339-2
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    References listed on IDEAS

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    1. Hesam N. Motlagh & James O. Wrabl & Jing Li & Vincent J. Hilser, 2014. "The ensemble nature of allostery," Nature, Nature, vol. 508(7496), pages 331-339, April.
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