Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation


The design and construction of biomimetic self-assembling systems is a challenging yet potentially highly rewarding endeavour that contributes to the development of new biomaterials, catalysts, drug-delivery systems and tools for the manipulation of biological processes. Significant progress has been achieved by engineering self-assembling DNA-, protein- and peptide-based building units. However, the design of entirely new, completely non-natural folded architectures that resemble biopolymers (‘foldamers’) and have the ability to self-assemble into atomically precise nanostructures in aqueous conditions has proved exceptionally challenging. Here we report the modular design, formation and structural elucidation at the atomic level of a series of diverse quaternary arrangements formed by the self-assembly of short amphiphilic α-helicomimetic foldamers that bear proteinaceous side chains. We show that the final quaternary assembly can be controlled at the sequence level, which permits the programmed formation of either discrete helical bundles that contain isolated cavities or pH-responsive water-filled channels with controllable pore diameters.

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Figure 1: Quaternary assemblies formed from short water-soluble oligourea foldamers.
Figure 2: Solution and solid-state studies of the formation of the oligourea helical bundle.
Figure 3: Solution and solid-state studies of channel-forming oligourea foldamers H2 and H5.
Figure 4: Control of the quaternary arrangement of oligourea foldamers through manipulation of the primary sequence.


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This work was funded in part by the CNRS and Conseil Regional d'Aquitaine (Project No. 20091102003). A pre-doctoral fellowship from the University of Bordeaux (to J.F.), CIFRE support from UREkA and ANRT (to L.M.) and Marie Curie FP7-PEOPLE-2010-IEF-273224 and FP7-PEOPLE-2012-IEF-330825 postdoctoral fellowships (to K.P.-Z. and C.M.L.) are gratefully acknowledged. We thank SOLEIL synchrotron and the ERSF for providing access to synchrotron facilities (beam lines PROXIMA 1, ID23-2 and ID29), and are grateful to P. Legrand for assistance on PROXIMA 1.

Author information

G.W.C. and G.G. conceived and designed the experiments. K.P.-Z., C.M.L., J.F. and L.M. synthesized and characterized the monomers and the oligomers used in this study. G.W.C. performed the crystallization experiments, collected X-ray data, solved and refined the crystal structures and performed the CD experiments. G.W.C., F.R. and V.G. designed and performed the mass spectrometry experiments. C.D.M. designed and performed the NMR spectroscopy experiments. M.D. and O.L. designed and performed the microscopy experiments. G.W.C., F.R., M.D., O.L., V.G., C.D.M. and G.G. analysed and interpreted the experimental data. G.W.C. and G.G. prepared the manuscript. All the authors reviewed and contributed to the manuscript.

Correspondence to Gilles Guichard.

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Competing interests

G.G. is cofounder of UREkA SARL and has financial interests in the company. The other authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 4097 kb)

Supplementary information

Structure factors file for H1 (CIF 6443 kb)

Supplementary information

Crystallographic data for H1 (CIF 15 kb)

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Structure factors file for H2 (CIF 6412 kb)

Supplementary information

Crystallographic data for H2 (CIF 15 kb)

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Structure factors file for H4 (CIF 790 kb)

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Crystallographic data for H4 (CIF 14 kb)

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Structure factors file for H5 (CIF 10365 kb)

Supplementary information

Crystallographic data for H5 (CIF 16 kb)

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Collie, G., Pulka-Ziach, K., Lombardo, C. et al. Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation. Nature Chem 7, 871–878 (2015).

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