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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.

Author information

1
School of Chemistry, University of Bristol , Cantock's Close, Bristol, BS8 1TS, United Kingdom.
2
Bristol Centre for Functional Nanomaterials, University of Bristol, Tyndall Avenue, Bristol, BS8 1FD, United Kingdom.
3
Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center , Leiden, The Netherlands.
4
School of Biochemistry, University of Bristol , Medical Sciences Building, University Walk, Bristol, BS8 1TD, United Kingdom.
5
School of Life Sciences, University of Sussex , Falmer, Brighton, East Sussex, BN1 9QG, United Kingdom.
6
BrisSynBio, University of Bristol , Life Sciences Building, Tyndall Avenue, Bristol, BS8 1TQ, United Kingdom.

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.

PMID:
26219086
DOI:
10.1021/jacs.5b03973
[Indexed for MEDLINE]

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