Title: Peptide foldamer-based nanostructures

Funding: The Polish National Science Centre (NCN, Poland), SONATA

Project number: 2017/26/D/ST5/00341

Cost: PLN 630 500.00

Duration: 04.06.2018-03.12.2021

Abstract:  Bionanomaterials are one of the fastest growing fields of material engineering. Materials based on self-organizing structures, i.e. nucleic acids, carbohydrates or peptides, deserve special attention. Especially self-assembled peptides possess a number of advantages over other organic and inorganic aggregates such as biocompatibility, ease of synthesis, and low toxicity. The possibility of modifying the chemical properties of peptides, e.g. by introducing unnatural amino acid residues into the sequence, provides them with various properties and a wide potential application. However, only the ability to strictly control the process of self-assembly of peptides, and in particular the ability to influence the type and size of the resulting nanostructures, can guarantee the formation of bionanomaterials with application in nanotechnology and synthetic biology. The peptide foldamers studied by us contain cyclic beta-amino acid residues in their structure and are oligomers with a well-defined structure in a solution, the preparation, characterization and process of controlled aggregation of which are of constant interest. Therefore, the main goal of this project was the rational design, synthesis and characterization of alpha, beta-peptide foldamers and their use as structural elements of higher order nanostructures created in the process of controlled self-assembly. This project goal can be considered fully achieved. In addition, it was possible to optimize various experimental methods for the study of peptide foldamers (e.g. analytical ultracentrifugation), to control the formation of aggregates (e.g. vibrational spectroscopy) and to characterize the obtained nanostructures (e.g. microscopic methods). The assumed goals have been achieved and the results have been published or are being published. The great advantage of the research carried out as part of this project is their interdisciplinary, which influences many fields of science, mainly in the field of chemical sciences and nanomaterials, but also translates into the development of research techniques and analysis of experimental data. The novelty of the research proposed in this project includes, first of all, a rational and systematic approach to the design of alpha, beta-peptides and research on the conditions and mechanism of their aggregation, as well as the type of nanostructures created, which is a significant impact on the development of the represented discipline. The results of the project will have a significant impact on the development of the scientific field, because they fill the gap which is the lack of systematized knowledge about the controlled aggregation of complex peptide structures (especially peptides containing cyclic beta-amino acid residues). In addition, optimization of the synthesis and purification methods of the so-called "difficult sequences" is a contribution to the development of research on amyloidogenic peptides. Moreover, the studied topic has great potential, therefore the research initiated thanks to the grant will be continued.

Publications:

1. Szefczyk, N. Szulc, M. Gasior-Glogowska, A.Modrak-Wojcik, A. Bzowska, W. Majstrzyk, M. Taube, M. Kozak, T. Gotszalk, E. Rudzinska-Szostak, L. Berlicki, Hierarchical Approach for the Rational Construction of Helix-Containing Nanofibrils Using α,β-Peptides, Nanoscale 2021, 13, 4000–4015.
2. Szefczyk, Peptide foldamer-based self-assembled nanostructures containing cyclic beta-amino acids, Nanoscale 2021,13, 11325–11333.
3. Szulc, M. Gąsior-Głogowska, J. W. Wojciechowski, M. Szefczyk, A. Żak, M. Burdukiewicz, M. Kotulska, Variability of amyloid propensity in imperfect repeats of CsgA protein of Salmonella enterica and Escherichia coli, Int. J. Mol. Sci. 2021, 22(10), 5127.
4. Dyrka, M. Gąsior-Głogowska, M. Szefczyk, N. Szulc, Searching for universal model of amyloid signaling motifs using probabilistic context-free grammars, BMC Bioinformatics 2021, 22, 222.
5. Gąsior-Głogowska M.E., Szulc N., Szefczyk M. (2022) Challenges in Experimental Methods. In: Li M.S., Kloczkowski A., Cieplak M., Kouza M. (eds) Computer Simulations of Aggregation of Proteins and Peptides. Methods in Molecular Biology 2022, vol 2340. Humana, New York, NY. pp 281-307.
6. Szefczyk, K. Ożga, M. Drewniak-Świtalska, E. Rudzińska-Szostak, R. Hołubowicz, A. Ożyhar, Ł. Berlicki, Controlling the conformational stability of coiled-coil peptides by a single stereogenic center of terminal β-amino acid residue. RSC Adv. 2022, 12, 4640-4647.
7. The application of the hierarchical approach for the construction of foldameric peptide self-assembled nanostructures, Monika Szefczyk, Natalia Szulc, Marlena Gąsior-Głogowska, Dominika Bystranowska, Andrzej Żak, Andrzej Sikora,  Oliwia Polańska, Andrzej Ożyhar, Łukasz Berlicki Soft Matter 2023.