MuST ArtEM | Multicomponent Supramolecular Structures as Artificial Enzyme Mimics

Summary
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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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101151996
Start date: 03-06-2024
End date: 02-06-2026
Total budget - Public funding: - 187 624,00 Euro
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Original description

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.

Status

SIGNED

Call topic

HORIZON-MSCA-2023-PF-01-01

Update Date

29-09-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2023-PF-01
HORIZON-MSCA-2023-PF-01-01 MSCA Postdoctoral Fellowships 2023