An Exploration of Short Peptoid Oligomers for the Assembly of Supramolecular Structures

Amphiphilic peptoids, sequence-defined synthetic polymers based on N-substituted glycines, demonstrate exceptional versatility in self-assembling into a variety of supramolecular structures, such as nanohelices¹, nanotubes², and nanosheets³. Their final morphologies are largely governed by the molecular packing of hydrophobic domains, which can be controlled by adjusting the composition and location of specific hydrophobic side chains.^1,4 Understanding the relationship between these building blocks and the resulting structures enables fine-tuned control over peptoid hierarchical assembly. In this presentation, I will discuss our team’s recent studies on the design of a series of amphiphilic peptoid oligomers that assemble into various supramolecular structures, including nanotubes, nanohelices and nanosheets. We demonstrate that the incorporation of a chiral polar side chain group can disrupt the peptoid assembly pathway. For example, the peptoid sequence Npm4Nc2-L-Ala forms right-handed twisted ribbons, achieving a more homogeneous distribution of polar groups in aqueous solution, while Npm4Nc2-D-Ala forms left-handed twisted ribbons.⁵ A single L- or D-Ala sequence can achieve multiple morphologies at different locations of the self-assembly energy landscape in a controllable manner with the change of assembly conditions. In contrast, the sequence Npm4 assembles into nanosheets. These distinct morphologies highlight the critical roles of polarity and chirality in peptoid self-assembly. We also demonstrated the assembly of crystalline nanosheets from C3-symmetric peptoids and other multiblock sequences, highlighting the opportunity of exploiting short peptoid oligomers for the assembly of supramolecular structures and developing multifunctional material. These findings provide valuable insights for future design strategies of peptoid sequences, supporting the possibility of achieving precise control over the self-assembly of sequence-defined synthetic polymers into functional materials.