Journal of the American Chemical Society 2015-08-26

Modular Design of Self-Assembling Peptide-Based Nanotubes.

Natasha C Burgess, Thomas H Sharp, Franziska Thomas, Christopher W Wood, Andrew R Thomson, Nathan R Zaccai, R Leo Brady, Louise C Serpell, Derek N Woolfson

Index: J. Am. Chem. Soc. 137 , 10554-62, (2015)

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Abstract

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.