Abstract
Nature has, through billions of years of evolution, assembled a multitude of polymeric macromolecules capable of exquisite molecular recognition. This functionality arises from the precise control exerted over their biosynthesis that results in key residues being anchored in the appropriate positions to interact with target substrates. Developing 'wholly synthetic' macromolecular analogues that can mimic this behaviour presents a considerable challenge to chemists, who lack the 'biological machinery' used in nature to assemble polymers with such precision. In addressing this challenge, familiar chemical concepts, such as combinatorial methods and supramolecular interactions, have been adapted for application in the macromolecular arena. Working from a limited set of residues, synthetic macromolecules have been produced that display surprisingly high binding affinities towards target proteins, even possessing useful in vivo activities. These observations are all the more surprising when one considers the heterogeneity inherent within these synthetic macromolecular receptors, and provoke intriguing questions regarding our assumptions about the design of receptors.
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We acknowledge the financial support of the Engineering and Physical Sciences Research Council (EP/G066507/1).
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C.S.M. and D.A.F. contributed equally to the writing of this article.
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Mahon, C., Fulton, D. Mimicking nature with synthetic macromolecules capable of recognition. Nature Chem 6, 665–672 (2014). https://doi.org/10.1038/nchem.1994
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DOI: https://doi.org/10.1038/nchem.1994
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