Periodic Reporting for period 2 - SENSE (Supramolecular Engineering of biologically iNSpired peptide nanostructurEs)
Okres sprawozdawczy: 2021-08-01 do 2023-01-31
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.
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.
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.