Supramolecular Engineering of biologically iNSpired peptide nanostructurEs

Informations projet

SENSE

N° de convention de subvention: 851179

DOI

10.3030/851179

Projet clôturé

Date de signature de la CE 16 Octobre 2019

Date de début 1 Février 2020

Date de fin 31 Janvier 2026

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 494 375,00

Contribution de l’UE

€ 1 494 375,00

Coordonné par

UNIVERSIDADE DA CORUNA
Spain

Periodic Reporting for period 3 - SENSE (Supramolecular Engineering of biologically iNSpired peptide nanostructurEs)

Période du rapport: 2023-02-01 au 2024-07-31

Résumé du contexte et des objectifs généraux du projet

Nanotechnology has the potential to revolutionize society in many key areas, including the development of new materials, processes, and products. For example, in the field of medicine, the use of nanotechnology currently spans several applications, ranging from regenerative medicine to the development of new therapeutics, imaging and diagnostic tools. Beyond these applications, one of the greatest challenges in the field is the design of complex and structurally well-defined smart materials with multiple functions that replicate the adaptive and dynamic properties of the biomolecular assemblies in living organisms. These properties allow living cells to sense specific stimuli and adapt to their needs by tuning the properties, structure, and function of their dynamic assemblies.
Therefore, meeting these challenges will afford new materials with improved structural control that can respond to specific stimuli (such as pH alterations, redox changes, enzyme activity, etc.) and deliver groundbreaking properties and functionalities that will open new research fields and impact both basic and applied sciences. Considering the field of medicine, these new materials can be applied for the development of smart delivery systems, which discriminate between healthy and diseased tissues and efficiently internalize into cells to improve delivery of drugs, or bioactive platforms that change their signaling properties reacting to external stimuli to induce specific cellular responses (e.g. cell differentiation, proliferation, etc.), ultimately improving people’s quality of life.
The overall objective of SENSE is to engineer complex and responsive multifunctional nanostructures that can be controlled on demand, from a bottom-up approach using simple components. Towards this end, we intend to use designed peptides in combination with the tools of metal coordination, supramolecular and dynamic covalent chemistries. This approach will allow us to obtain new smart materials with potential applications in the biomedicine field, as bioactive platforms or drug delivery systems, thanks to the inherent biocompatibility and biodegradability of peptide-based materials.

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

In the SENSE project, we are applying well-known tools in the field of chemistry to develop complex and well-defined nanostructures that can be controlled on demand. We intend to apply these peptide-based materials as smart delivery systems, improved bioactive scaffolds or artificial adaptor nanostructures in living cells. This project lies on our combined experience in organic synthesis, supramolecular chemistry, chemical biology, and peptide materials.
We have synthesized several peptide sequences that incorporate different moieties, such as aldehydes, hydrazines, thiols, bipyridinium derivatives or metal chelators, and we have observed that under adequate conditions these peptide derivatives self-assemble into highly homogeneous and long nanofibers. Interestingly, preliminary results show that the nanostructures are nontoxic to eukaryotic cells, suggesting that these materials have the potential of being used for biomedical applications. We are now trying to control their assembly under different stimuli, and some preliminary results indicate that the assembly of the fibers is reversible and therefore, these stimuli could be used to control the structure and the biological activity of the fiber.
On the other hand, we are also synthesizing new peptide moieties that in combination with appropriate macrocyclic receptors can yield supramolecular switches. These new supramolecular systems can be used to control peptide aggregation/assembly. So far, we have synthesized several derivatives that form supramolecular complexes with different macrocyclic receptors. Interestingly, preliminary studies show that the supramolecular complexes can be modified with external stimuli, what makes them a promising tool to control peptide self-assembly when incorporated in certain peptide sequences.

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)

As a result of this first period of the project, we have developed new peptide derivatives that self-assemble into highly homogeneous nanofibers, differentiating from the most common self-assembled peptide nanostructures that rely on the use of stackable motifs. Thanks to the modifications introduced in the peptide sequences, these nanostructures have the capacity of being controlled under different conditions and, so far, we have demonstrated that they are nontoxic towards eukaryotic cells. Therefore, these peptide-based materials can be modified to achieve precise nanoscale control over the presentation of bioactive molecules yielding multivalent nanostructures that can be applied in the biomedical field as smart delivery vehicles or improved bioactive scaffolds. Furthermore, these new peptide-based platforms can also be exploited for the development of other complex 2D and 3D materials with applications in other fields, such as biotechnology or organic bioelectronics.
We have also developed new peptide-based supramolecular switches that can be incorporated into peptide sequences, expanding the already existing tools in the field of supramolecular chemistry. These new supramolecular switches will be exploited to control the formation of the nanostructures with external stimuli and can be also incorporated in other systems to modify their biological functions, aggregation state, structure, etc.