The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control molecular 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 known and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner, but it remains challenging to design these so-called 'foldamers' so that they are capable of inducing or controlling chemical processes and interactions. 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 equilibrium 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 molecules, 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.
Bibliographical noteFunding Information:
We thank T. Senthil, M.P.A. Fisher, S. Sachdev, S. Kivelson, P.A. Lee, R.B. Laughlin and P.W. Anderson for discussions, and R. Lee for technical assistance. This work was supported by NSF CAREER and MRSEC grants, a Terman fellowship, the Natural Science and Engineering Research Council of Canada, the Canadian Institute for Advanced Research and the Institute for Theoretical Physics.
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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