Hydrophobicity-Controlled Self-Assembly of Supramolecular Peptide Nanotubes in Water

Polymer-conjugated peptides are attractive building blocks for the construction of new nanomaterials. However, the ability to control the self-assembly of these materials remains a major limitation to their wider utilization. Herein, we report a facile strategy to fine-tune the assembly of water-soluble hydrophilic polymer-conjugated cyclic peptides by incorporating a defined, short hydrocarbon linker between the polymer and peptide. This addition creates a well-defined hydrophobic "inner shell" that suppresses water from disrupting the organized peptide hydrogen bond network. Our approach is demonstrated using a series of cyclic peptide-linker-PDMA conjugates that were evaluated by asymmetric flow field flow fractionation, small angle neutron scattering and transmission electron microscopy. Molecular dynamics simulations were also used to show how the polymer and the peptide stacks interact and illustrate the impact of this hydrophobic inner shell approach. This strategy provides a modular approach to fine control the nanotube self-assembling behavior. We expect that this technique will improve the versatility of peptide nanotubes for the engineering of advanced nanomaterials.