Multicomponent supramolecular wires as a platform for the control of protein functions

Informations projet

SupramolecularWires

N° de convention de subvention: 749919

DOI

10.3030/749919

Projet clôturé

Date de signature de la CE 20 Février 2017

Date de début 1 Avril 2017

Date de fin 31 Mars 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 165 598,80

Contribution de l’UE

€ 165 598,80

Coordonné par

TECHNISCHE UNIVERSITEIT EINDHOVEN
Netherlands

Periodic Reporting for period 1 - SupramolecularWires (Multicomponent supramolecular wires as a platform for the control of protein functions)

Période du rapport: 2017-04-01 au 2019-03-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The synthesis of the hybrid supramolecular wires was achieved and a general protocol for the characterisation of the individual components was stablished using agarose gel electrophoresis, ES-MS and absorbance spectroscopy. Technical reports regarding these optimised protocols for the synthesis of the hybrid supramolecular wires and their correct assembly into a functional structure were stablished and published in peer review journals.Short communications, results and major discoveries were presented at relevant the following meetings and international conferences.Study of the multivalent effect on the supramolecular 1-D displays was investigated revealing superselectivity towards multivalent targets. The use of DNA allowed the characterisation of highly dynamic supramolecular assemblies using TEM. This was the first time that such structures have been directly characterised. The results obtained in this project revealed novel features of multivalent dynamic systems: Noncovalent self-assembled 1-D structures can behave effectively as multivalent displays. The use of DNA as a linkage allows fine tuning of the strength of the interactions and also multiplexing. Superselectivity can be observed in 1-D dynamic systems such as supramolecular polymers.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The project achieved several milestones in the development of functional synthetic biological systems. Some of the most remarkable results are the establishment of self-assembled 1-D as platforms for binding of biomolecules. The use of DNA facilitated the synthesis and allows the synthesis of multi component systems.Current work is focusing on the integration of enzymes into the 1-D platform. This system can be envisioned as enzyme platform for cascade reactions for the production of commercially relevant substances such as metabolites, drugs, and fuel molecules.

Schematic representation of the multivalent 1-D display