De NovoDesigned Peptide and Protein Hairpins Self-assemble into Sheets and Nanoparticles

Abstract

The design and assembly of peptide based materials has advanced considerably, leading to a variety of fibrous, sheet and nanoparticle structures. A remaining challenge is to account for and control different possible supramolecular outcomes accessible to the same or similar peptide building blocks. Here we present a straightforward de novo peptide system that forms nanoparticles or sheets depending on the strategic placement of a ‘disulfide pin’ between two elements of secondary structure that drive self-assembly. Specifically, we joined a homodimerizing and a homotrimerizing de novo coiled-coil α-helices with a flexible linker to generate a series of linear peptides. These helices were then pinned back-to-back and so constrained into a hairpin shape by a disulfide bond placed either proximal or distal to the linker. Computational modeling and extensive observations by advanced microscopy show that the proximally pinned hairpins self-assemble into nanoparticles, whereas the distally pinned constructs form sheets. These peptides can be made synthetically or recombinantly to allow both chemical modifications and the introduction of whole protein cargoes as required.

The Application of Nanotechnology for Quantification of Circulating Tumour DNA in Liquid Biopsies: A Systematic Review

“…Nanostructures made entirely from peptides [73] have not yet been explored widely for ctDNA analysis. Generally, they are less well-established than their DNA counterparts because interactions between peptides are more difficult to predict than DNA base-pairing.…”