Modular design of self-assembling peptide-based nanotubes

Burgess, N. C., Sharp, T. H., Thomas, F., Wood, C. W., Thomson, A. R. , Zaccai, N. R., Brady, R. L., Serpell, L. C. and Woolfson, D. N. (2015) Modular design of self-assembling peptide-based nanotubes. Journal of the American Chemical Society, 137(33), pp. 10554-10562. (doi: 10.1021/jacs.5b03973) (PMID:26219086)

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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.

Item Type:Articles
Additional Information:N.C.B. thanks the EPSRC-funded Bristol Centre for Functional Nanomaterials Centre for Doctoral Training for a postgraduate scholarship (EP/G036780/1). F.T. and D.N.W. thank the Leverhulme Trust for funding (RPG-2012-536). D.N.W. holds a Royal Society Wolfson Research Merit Award.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Dr Drew
Authors: Burgess, N. C., Sharp, T. H., Thomas, F., Wood, C. W., Thomson, A. R., Zaccai, N. R., Brady, R. L., Serpell, L. C., and Woolfson, D. N.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Journal of the American Chemical Society
Publisher:American Chemical Society
ISSN:0002-7863
ISSN (Online):1520-5126
Published Online:28 July 2015

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