Abstract
The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control mo-lecular association, catalysis, self-replication or other chemical processes. In the case of proteins in particular, the dependence of these functions on the three-dimensional protein conformation is long known1 and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner2,3,4,5,6,7, but it remains challenging to design these so-called ‘foldamers’ so that they are capable of inducing or controlling chemical processes and interactions8,9. Here we show that the stability gained from folding can be used to control the synthesis of oligomers from short chain segments reversibly ligated through an imine metathesis reaction. That is, folding shifts the ligation equilibrium10,11,12,13 in favour of conformationally ordered sequences, so that oligomers having the most stable solution structures form preferentially. Crystallization has previously been used to shift an equilibrium in order to indirectly influence the synthesis of small molecules14, but the present approach to selectively prepare macromolecules with stable conformations directly connects folding and synthesis, emphasizing molecular function rather than structure in polymer synthesis.
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Acknowledgements
We thank C. F. Zukoski and A. Y. Mirarefi for discussions and comments on light-scattering experiments. This work was supported by the National Science Foundation and the US Department of Energy, Division of Materials Sciences, through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign.
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Supplementary information
41586_2001_BF414889a_MOESM2_ESM.pdf
Solvent denaturation, CD and molecular modeling of imine dodecamer 3e and imine metathesis for folding-driven synthesis of oligomers (PDF 41 kb)
41586_2001_BF414889a_MOESM3_ESM.pdf
Theoretical consideration of the segment selection and the driving force of the equilibrium shifting for folding-driven systems of oligomers (PDF 142 kb)
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Oh, K., Jeong, KS. & Moore, J. Folding-driven synthesis of oligomers. Nature 414, 889–893 (2001). https://doi.org/10.1038/414889a
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DOI: https://doi.org/10.1038/414889a
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