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J Am Chem Soc. 2015 Aug 26;137(33):10554-62. doi: 10.1021/jacs.5b03973. Epub 2015 Aug 12.

Modular Design of Self-Assembling Peptide-Based Nanotubes.

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School of Chemistry, University of Bristol , Cantock's Close, Bristol, BS8 1TS, United Kingdom.
Bristol Centre for Functional Nanomaterials, University of Bristol, Tyndall Avenue, Bristol, BS8 1FD, United Kingdom.
Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center , Leiden, The Netherlands.
School of Biochemistry, University of Bristol , Medical Sciences Building, University Walk, Bristol, BS8 1TD, United Kingdom.
School of Life Sciences, University of Sussex , Falmer, Brighton, East Sussex, BN1 9QG, United Kingdom.
BrisSynBio, University of Bristol , Life Sciences Building, Tyndall Avenue, Bristol, BS8 1TQ, United Kingdom.


An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens.

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