title: Nucleobase-directed amyloid nanotube assembly.
abstract: Cytosine nucleobases were successfully incorporated into the side chain of the self-assembling amyloid peptide fragment HHQALVFFA to give ccAQLVFFA. At a pH range of 3-4, where cytosine is expected to be partially protonated, small-angle X-ray scattering analyses revealed the nucleobase peptide assembles to be well-defined nanotubes with an outer diameter of 24.8 nm and wall thicknesses of 3.3 nm. FT-IR and X-ray diffraction confirmed beta-sheet-rich assembly with the characteristic cross-beta architecture of amyloid. The beta-sheet registry, determined by measuring (13)CO-(13)CO backbone distances with solid-state NMR and linear dichroism, placed the cytosine bases roughly perpendicular to the nanotube axis, resulting in a model where the complementary interactions between the cytosine bases increases beta-sheet stacking to give the nanotube architecture. These scaffolds then extend the templates used to encode biological information beyond the nucleic acid duplexes and into covalent networks whose self-assembly is still defined by a precise complementarity of the side-chain registry.
authors.affiliation: Center for Fundamental and Applied Molecular Evolution, Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Ni
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mehta
authors.forename: W Seth
authors.initials: WS
authors.lastname: Childers
authors.forename: Ami
authors.initials: A
authors.lastname: Lakdawala
authors.forename: Sai Venkatesh
authors.initials: SV
authors.lastname: Pingali
authors.forename: Pappannan
authors.initials: P
authors.lastname: Thiyagarajan
authors.forename: David G
authors.initials: DG
authors.lastname: Lynn
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D003198:Computer Simulation; D006860:Hydrogen Bonding; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008968:Molecular Conformation; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D013057:Spectrum Analysis
chemical_list: D000682:Amyloid