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Publication - Professor Leo Brady

    Modular Design of Self-Assembling Peptide-Based Nanotubes


    Burgess, NC, Sharp, TH, Thomas, F, Wood, CW, Thomson, AR, Zaccai, NR, Brady, RL, Serpell, LC & Woolfson, DN, 2015, ‘Modular Design of Self-Assembling Peptide-Based Nanotubes’. Journal of the American Chemical Society, vol 137., pp. 10554-10562


    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.

    Full details in the University publications repository