Many of the promising applications of (bio)nanotechnology rely on extending synthetic organic chemistry at the nanometer length-scale to deliver materials with distinctive properties and function. Sequence-specific molecules, exhibiting a water soluble potential (e.g. biopolymers) have advantages as design elements for construction of these types of nanoscale materials in that correlations can be drawn between primary structure (i.e. the sequence), secondary structure (folded elements) and further assembly into higher order (tertiary and quaternary) structure, potentially affording ordered architectures with emergent functions tailored to various biotechnology and medical applications (e.g. encapsulation and release, sensing, storage, catalysis). Non-biological synthetic folded oligomers – i.e. foldamers – can be used to create both complex and atomically precise nanostructures, and allow the exploitation of a wide range of building units, enabling the creation of self-assembled supramolecular architectures that would differ fundamentally from nature in terms of topologies and emerging functions.
The general aim of this project was thus to create such protein-like quaternary structures by using (i) non-natural sequence-specific urea-based folded oligomers, and (ii) a fabrication process in aqueous conditions mimicking those at work in proteins (i.e. hierarchical structure formation). These oligourea foldamers possess specific advantages such as synthetic accessibility, high folding fidelity and stability to enzymatic proteolysis. In line with this general objective, the project was seeking a) to delineate the design principles leading to the formation of homogeneous assemblies of oligourea helices, b) to structurally elucidate the resulting nanostructures at the atomic level and c) to explore molecular recognition processes within such foldamer quaternary structures. The project capitalized on the discovery (published in Nature Chemistry in 2015) by the host group that properly designed water-soluble oligourea sequences were able to form well-defined compact or extended self-assembled nanostructures such as the six-helix bundle which was studied in more details in this project.
