Abstract

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix–turn–helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix–turn–helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

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Acknowledgements

This work was supported by the European Research Council under the European Union's Seventh Framework Programme (Grant Agreement no. ERC-2012-AdG-320892), by the European Union under the People program (FP7 PIIF-2009-254156 postdoctoral fellowship to T.Q.) and by the French–Chinese Foundation for Science and its Applications (postdoctoral fellowship to B.C.). The contribution of S. Post in optimizing the synthesis of 4-tBuO-protected quinoline monomers is acknowledged. The authors thank B. Kauffmann for assistance with X-ray data collection and structure resolution at the Institut Européen de Chimie et Biologie's X-ray diffraction facility and M. Ferrer for beam time and help during the data collection on FIP-BM30A at the European Synchrotron Radiation Facility.

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Author notes

    • Bo Chi
    •  & Ting Qi

    Present addresses: State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South Puzu Road, Pukou District, Nanjing 211816, China (B.C.); School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China (T.Q.).

Affiliations

  1. CBMN Laboratory, Université de Bordeaux, CNRS, IPB, Institut Européen de Chimie et Biologie, 2 rue Escarpit, 33600 Pessac, France

    • Soumen De
    • , Bo Chi
    • , Thierry Granier
    • , Ting Qi
    • , Victor Maurizot
    •  & Ivan Huc

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Contributions

S.D. and B.C. contributed equally to this work. S.D., B.C. and T.Q. synthesized all the new compounds, carried out the solution studies and grew single crystals. T.G. refined the crystal structures. I.H. and V.M. designed the research and carried out the modelling studies. I.H. wrote the manuscript. All the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ivan Huc.

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DOI

https://doi.org/10.1038/nchem.2854