FOLDASYNBIO · Bioinspired Nanostructures by Self-assembly of Amphiphilic Non-peptide Helical Foldamers in Aqueous Environment
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-09-01 → 2018-10-31
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Bioinspired Nanostructures by Self-assembly of Amphiphilic Non-peptide Helical Foldamers in Aqueous Environment
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.
Data: CORDIS, © European Union
Project objective
The design and precise construction of biomimetic self-assembling systems in aqueous solution is a challenging yet potentially highly rewarding endeavor, contributing to the development of new biomaterials, catalysts, drug-delivery systems and tools for the manipulation of biological processes. A high level of sophistication with control over morphologies and functions has been achieved by engineering self-assembling peptide-based building units. Although peptides possess a number of specific advantages including synthetic availability, modularity, one difficulty resides in precisely controlling the rules relating primary sequence and secondary structure. Alternatively, opportunities exist to develop bottom-up approaches using non-natural oligomers also referred to as foldamers, with predictable and well-defined folding patterns. Advances in foldamer chemistry bode well for their use as building units for the precise construction of nanometer scale assemblies and for possible applications. This project will move a step forward towards the realization of this mission, by developing protein-like quaternary arrangements under sequence based control using amphiphilic helical foldamers in aqueous conditions. The applicant has been trained in the synthesis of folded oligoamides and more importantly has acquired a high level of expertise in the design and structural characterization of peptide-based assemblies. He will join and bring his expertise to a host laboratory in France that has pioneered the development of urea-based helical foldamers. Secondment in one established European group with prominent expertise in X-ray crystallography techniques and biological structure determination will provide the appropriate combination of knowledge required for this multidisciplinary study. This approach will be a milestone in the design of foldamer-based quaternary architectures and may lead to new functional nanostructures.
Original text from CORDIS.
Participants
- UNIVERSITE DE BORDEAUX · BordeauxCoordinatorFrance
Links
Data: CORDIS, © European Union