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Folding-driven synthesis of oligomers

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 prot...

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Bibliographic Details
Published in:Nature (London) 2001-12, Vol.414 (6866), p.889-893
Main Authors: Moore, Jeffrey S, Oh, Keunchan, Jeong, Kyu-Sung
Format: Article
Language:English
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Summary: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 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/414889a