Peptide nanotube-based materials are an emerging field in chemical biology. Alternating D/L cyclic peptides are versatile materials that form ordered structures by stacking through backbone hydrogen bond interactions.1 The predictable and consistent formation of these supramolecular and macromolecular structures can potentially be used to generate synthetic functional proteins. Due to the self-driven nature of the nanotube assembly, one of the current major limitations is the lack of control over the assembly size which results in long fibrous networks. By overcoming this limitation, we propose that we can gain better control over the nanotube material properties.
One method to control nanotube assembly is to utilise sidechain functionality to form covalent bonds between cyclic peptide monomers.2 Controlled synthesis of cyclic peptide monomers can be achieved through an orthogonal protecting group strategy to selectively couple through various heterogenous and homogenous reactions. Covalently tethering cyclic peptides can limit the stacking and provide more control over selective modifications of the structure. In this work, we will discuss the synthetic approaches we have used to make covalently linked cyclic peptide nanotubes and the methods used to characterise the three-dimensional structures and properties of these materials.