title: Controlling the Assembly of Coiled-Coil Peptide Nanotubes.
abstract: An ability to control the assembly of peptide nanotubes (PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α-helical barrels with tunable internal cavities as building blocks. These first-generation designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm-long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs.
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.|Institute for Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors.forename: Franziska
authors.identifier: http://orcid.org/0000-0002-1176-7018
authors.initials: F
authors.lastname: Thomas
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.|Bristol Centre of Functional Materials, HH Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL, UK.
authors.forename: Natasha C
authors.identifier: http://orcid.org/0000-0002-3146-5295
authors.initials: NC
authors.lastname: Burgess
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
authors.forename: Andrew R
authors.identifier: http://orcid.org/0000-0002-1066-1369
authors.initials: AR
authors.lastname: Thomson
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. D.N.Woolfson@bristol.ac.uk.|School of Biochemistry, University of Bristol, Medical Science Building, University Walk, Bristol, BS8 1TD, UK. D.N.Woolfson@bristol.ac.uk.|BrisSynBio, University of Bristol, Life Science Building, Tyndall Avenue, Bristol, BS8 1TQ, UK. D.N.Woolfson@bristol.ac.uk.
authors.forename: Derek N
authors.identifier: http://orcid.org/0000-0002-0394-3202
authors.initials: DN
authors.lastname: Woolfson
mesh_terms: D046529:Microscopy, Electron, Transmission; D045333:Nanotubes, Peptide / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D045333:Nanotubes, Peptide
keywords: native chemical ligation; peptide nanotubes; self-assembly; transmission electron microscopy; α-helical barrels