SupramolecularWires · Multicomponent supramolecular wires as a platform for the control of protein functions
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-04-01 → 2019-03-31
- EU contribution
- €165,599
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Multicomponent supramolecular wires as a platform for the control of protein functions
The construction of synthetic systems that can replicate cellular components, and their integration into cells in order to rewire natural signal transduction systems, are two landmark objectives in the field of synthetic biology, and can be readily addressed by supramolecular chemists. Supramolecular systems en route to these goals have been recently reported. Nevertheless, the level of complexity and control is still in its infancy when compared to natural systems. Merging biological components such as oligonucleotides, with synthetic supramolecular systems, we stand to benefit from the exceptional structural and functional features of biological and synthetic building blocks while at the same time broadening their functionality. Thus, the general goal of this project was to shed light on the dynamic phenomena of multicomponent hybrid self-assembly processes. To achieve this aim supramolecular polymers were merged with DNA molecules. The supramolecular wire functions as a dynamic multiva-lent receptor. DNA is a suitable building block for the formation of multivalent ligands. The programmability and predictable assembly of DNA duplex formation allows the control of the distribution, orientation and density of the ligands in the scaffold. In particular the main objectives were to understand the influence of linking DNA to supramolecular systems. It was also investigated how this 1-D platforms can be used to display dynamic binding sites. These bioinspired functions also are expected to pave the way towards other emerging properties such as self-replication, and eventually the mimicking of the cellular life cycle in minimal life systems.
Data: CORDIS, © European Union
Project objective
Supramolecular chemistry offers a platform on which it is possible to engineer modular systems to gain further understanding of complex biological phenomena. The goal of this proposal is to bring supramolecular systems to a more advanced level of complexity by merging synthetic supramolecular structures with engineered proteins and oligonucleotides to generate hybrid supramolecular systems. A program based in five stages is described, where all the systems make use of the inherent dynamic nature of hybrid supramolecular wires to dictate control over protein functions. These architectures are based on disc-shaped molecules that self-assemble to form supramolecular wires, while maintaining the ability to exchange monomers after initial assembly. A covalent approach will be established in stage one, engineered proteins will be covalently attached to the discotic building blocks of the supramolecular wire. Their assembly along the supramolecular wire will induce protein activity, e.g. protease activation. In stage two, short oligonucleotides covalently attached to the discotic building blocks and to the proteins, will provide additional control over the final assembly. The topic of stage three is the recruitment of signalling proteins in a reversible manner by displaying short peptide binding motifs for specific protein binding domains. For stage four, supramolecular wires will exhibit small oligonucleotides that will bind reversibly to protein fusion-oligonucleotide hybrid constructs resulting in protein activation and signal transduction. A higher level of complexity will be explored in stage five, by decorating the supramolecular wires with a larger array of responsive peptide and DNA motifs. This work will contribute new concepts, tools, and materials for elucidation and modulation of biochemical pathways in cells and for bioanalyte detection in vitro, that will be of benefit to the biological community.
Original text from CORDIS.
Participants
- TECHNISCHE UNIVERSITEIT EINDHOVEN · EindhovenCoordinatorNetherlands
Links
Data: CORDIS, © European Union