Squaring the Circle in Peptide Assembly: From Fibers to Discrete Nanostructures by De Novo Design.

Aimee L. Boyle, Elizabeth H. C. Bromley*, Gail J. Bartlett, Richard B. Sessions, Thomas H. Sharp, Claire L. Williams, Paul M. G. Curmi, Nancy R. Forde, Heiner Linke, Derek N. Woolfson

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

69 Citations (Scopus)

Abstract

The design of bioinspired nanostructures and materials of defined size and shape is challenging as it pushes our understanding of biomolecular assembly to its limits. In such endeavors, DNA is the current building block of choice because of its predictable and programmable self-assembly. The use of peptide- and protein-based systems, however, has potential advantages due to their more-varied chemistries, structures and functions, and the prospects for recombinant production through gene synthesis and expression. Here, we present the design and characterization of two complementary peptides programmed to form a parallel heterodimeric coiled coil, which we use as the building blocks for larger, supramolecular assemblies. To achieve the latter, the two peptides are joined via peptidic linkers of variable lengths to produce a range of assemblies, from flexible fibers of indefinite length, through large colloidal-scale assemblies, down to closed and discrete nanoscale objects of defined stoichiometry. We posit that the different modes of assembly reflect the interplay between steric constraints imposed by short linkers and the bulk of the helices, and entropic factors that favor the formation of many smaller objects as the linker length is increased. This approach, and the resulting linear and proteinogenic polypeptides, represents a new route for constructing complex peptide-based assemblies and biomaterials.

Original languageEnglish
Article number123456
Pages (from-to)15457-15467
Number of pages11
JournalJournal of the American Chemical Society
Volume134
Issue number37
DOIs
Publication statusPublished - 19 Sep 2012

Structured keywords

  • Bristol BioDesign Institute

Keywords

  • HETERODIMERIC COILED-COIL
  • GCN4 LEUCINE-ZIPPER
  • SYNTHETIC BIOLOGY
  • PROTEIN FIBER
  • DNA
  • COLLAGEN
  • SEQUENCE
  • SPECIFICITY
  • SYMMETRY
  • HELICES

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