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Multicomponent Supramolecular Structures as Artificial Enzyme Mimics

Project description

Functional supramolecular polymers with emerging catalytic properties

Supramolecular polymers (SPs) enable the fabrication of functional and dynamic materials due to their noncovalent nature, which often leads to the emergence of novel properties. With the support of the Marie Skłodowska-Curie Actions programme, the MuST ArtEM project aims to develop functional SPs that act as artificial nucleases capable of recognising and cleaving RNA. These polymers are based on 1,3,5-benzenetricarboxyamide (BTA) embedded with a 1,4,7-triazacyclononane-zinc moiety (TACN-Zn2+), which enables oligonucleotide binding through electrostatic interactions and subsequent cleavage via cooperative catalysis. The system will be utilised to drive the operation of RNA-based nanodevices and networks, which will ultimately be employed for the development of catalytic organelles through liquid-liquid phase separation.

Objective

Supramolecular polymers (SPs) are at the forefront of current research to functional bio-mimetic materials and systems. Among the plethora of SPs appeared in the literature in the last decades, those based on 1,3,5-benzenetricarboxyamide (BTA), which have shown to form double helical fibres both in organic and aqueous solution, have been employed as a robust platform for the design of bio-inspired materials with tailored and tuneable properties. Indeed, non-covalent synthesis allows to easily obtain a wide range of functional SPs by simply mixing chemically distinct monomers in solution, which will spontaneously self-assemble into dynamic structures. Such approach has been exploited to develop BTA-based SPs able to bind nucleic acids in a superselective fashion through multivalent interactions between positively charged co-assembled BTA monomers and the phosphate present in the oligonucleotide backbone. Building on these previous findings, MuST ArtEM aims to develop functional SPs to be exploited as artificial nucleases, able to recognize and cleave RNA. The recognition and the hydrolytic activity are provided by cationic components bearing the 1,4,7-triazacyclononane-zinc complexes (TACN-Zn2+), which is well known to catalyse the hydrolysis of phosphodiester bonds. The positively charged components undergo clustered upon binding with the oligonucleotide, thus enhancing the hydrolytic ability of the zinc complex through cooperative catalysis. Once degraded, the RNA is no more able to induce clustering of the functional monomers, which will come back to the initial random distribution, switching off the catalytic ability of the fibres. Such functional SPs will be then tested in more complex systems, to trigger downstream self-assembly of DNA structures. Finally, liquid-liquid phase separation of the functional SPs will be achieved, developing bio-inspired compartmentalized hydrolytic microreactors.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

TECHNISCHE UNIVERSITEIT EINDHOVEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 187 624,32
Address
GROENE LOPER 3
5612 AE Eindhoven
Netherlands

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Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
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Total cost

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