Nanostructures based on peptide foldamers

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Principal Investigator: Monika Szefczyk

Team:

Ewa Rudzińska-Szostak, PhD, D.Sc.

Daniel Wiczew, MSc, Eng.

Magda Drewniak-Świtalska, Ph.D, Eng.

Scientific Cooperation:

Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology:

Małgorzata Kotulska, PhD, D.Sc, Eng; Marlena Gąsior-Głogowska, PhD, Eng; Natalia Szulc, MSc, Eng.

FTIR, RAMAN

Faculty of Microsystem Electronics and Photonics, Wroclaw University of Science and Technology:

Teodor Gotszalk, PhD, D.Sc, Eng; Krzysztof Gajewski, PhD, Eng; Wojciech Majstrzyk, MSc, Eng. AFM

Faculty of Mechanical Engeineering, Wroclaw University of Science and Technology:

Andrzej Żak, PhD, Eng;

TEM

Division of Biophysics, Faculty of Physics, Institute of Experimental Physics, University of Warsaw,

Agnieszka Bzowska, , PhD, D.Sc; Anna Modrak-Wójcik, PhD

AUC

Faculty of Biochemistry, Molecular Biology and Biotechnology, Wroclaw University of Science and Technology:

Rafał Hołubowicz, PhD, Eng;


Project financed by: National Science Centre, no. 2017/26/D/ST5/00341

Start date: June 2018

Project duration: 36 months

Budget: 630 500,00 zł


Abstract

Bionanomaterials are nowadays one of the fastest growing research area of material engineering. Special attention has been paid to the materials composed of self-organizing structures, such as nucleic acids, hydrocarbons and peptides. Particularly, self-assembling peptides have revealed many advantages over other organic and inorganic aggregates, for instance biological compatibility, rather simple synthesis and low toxicity. Moreover, vast possibility of peptides chemical properties modulation guarantees a range of possible applications. As so, bionanomaterials based on peptide nanostructures have shown to entrap many different bioactive molecules with a controlled release pattern, thus can be applied as drug delivery systems. However, only ability to rational control over the assembly formation, especially influence on type and size of obtained nanostructures, will provide bionanomaterials useful for applications in nanotechnology and synthetic biology.

The main goal of the project involves rational design of peptide foldamers to be exploited as building blocks for the controlled self-assembly of nanomaterials. Foldamers are oligomers that exhibit a define tendency to folding to stable 3D structure in solution and possess enormous potential among synthetic self-organizing systems to mimic the regular structural behavior of biomolecules. Virtually unexplored is a subject of self-organization of complex α,β-peptides. That is why, there will be carried out studies in order to increase knowledge regarding design, synthesis and aggregation of peptides containing both α- and β-residues, which can be potentially applied in the synthesis of bionanomaterials with a vast range of applications.

Conference communications

  1. 25th Polish Peptide Symposium, Wojanów, 8-12.09.2019 - poster "Enhancing the stability and self-assembly of short coiled-coil peptides by introducing cyclic β-amino acids".

Publications

  • Szefczyk, M.; Ożga, K.; Drewniak-Świtalska, M.; Rudzińska-Szostak, E.; Hołubowicz, R.; Ożyhar, A.; Berlicki, Ł., Controlling the conformational stability of coiled-coil peptides with a single stereogenic center of a peripheral β-amino acid residue RSC Adv. 2022, 12, 4640. View at Publisher
    Abstract

    The key issue in the research on foldamers remains the understanding of the relationship between the monomers structure and conformational properties at the oligomer level. In peptidomimetic foldamers, the main goal of which is to mimic the structure of proteins, a main challenge is still better understanding of the folding of peptides and the factors that influence their conformational stability. We probed the impact of the modification of the peptide periphery with trans- and cis-2-aminocyclopentanecarboxylic acid (ACPC) on the structure and stability of the model coiled-coil using circular dichroism (CD), analytical ultracentrifugation (AUC) and two-dimensional nuclear magnetic resonance spectroscopy (2D NMR). Although, trans-ACPC and cis-ACPC-containing mutants differ by only one peripheral stereogenic center, their conformational stability is strikingly different..
  • Szefczyk, M.; Szulc, N.; Gąsior-Głogowska, M.; Modrak-Wójcik, A.; Bzowska, A.; Majstrzyk, W.; Taube, M.; Kozak, M.; Gotszalk, T.; Rudzińska-Szostak, E.; Berlicki, Ł., Hierarchical approach for the rational construction of helix-containing nanofibrils using α,β-peptides. Nanoscale 2021, 13, 4000. View at Publisher
    Abstract

    The rational design of novel self-assembled nanomaterials based on peptides remains a great challenge in modern chemistry. A hierarchical approach for the construction of nanofibrils based on α,β-peptide foldamers is proposed. The incorporation of a helix-promoting trans-(1S,2S)-2-aminocyclopentanecarboxylic acid residue in the outer positions of the model coiled-coil peptide led to its increased conformational stability, which was established consistently by the results of CD, NMR and FT-IR spectroscopy. The designed oligomerization state in the solution of the studied peptides was confirmed using analytical ultracentrifugation. Moreover, the cyclopentane side chain allowed additional interactions between coiled-coil-like structures to direct the self-assembly process towards the formation of well-defined nanofibrils, as observed using AFM and TEM techniques..
  • Szulc, N.; Gąsior-Głogowska, M.; Wojciechowski, J. W.; Szefczyk, M.; Żak, A.; Burdukiewicz, M.; Kotulska, M., Variability of amyloid propensity in imperfect repeats of CsgA protein of Salmonella enterica and Escherichia coli Int. J. Mol. Sci. 2021, 22, 5127. View at Publisher
    Abstract

    CsgA is an aggregating protein from bacterial biofilms, representing a class of functional amyloids. Its amyloid propensity is defined by five fragments (R1–R5) of the sequence, representing non-perfect repeats. Gate-keeper amino acid residues, specific to each fragment, define the fragment’s propensity for self-aggregation and aggregating characteristics of the whole protein. We study the self-aggregation and secondary structures of the repeat fragments of Salmonella enterica and Escherichia coli and comparatively analyze their potential effects on these proteins in a bacterial biofilm. Using bioinformatics predictors, ATR-FTIR and FT-Raman spectroscopy techniques, circular dichroism, and transmission electron microscopy, we confirmed self-aggregation of R1, R3, R5 fragments, as previously reported for Escherichia coli, however, with different temporal characteristics for each species. We also observed aggregation propensities of R4 fragment of Salmonella enterica that is different than that of Escherichia coli. Our studies showed that amyloid structures of CsgA repeats are more easily formed and more durable in Salmonella enterica than those in Escherichia coli. .
  • Szefczyk M., Peptide foldamer-based self-assembled nanostructures containing cyclic beta-amino acids Nanoscale 2021, 13, 11325. View at Publisher
    Abstract

    Peptide soft materials belong to an emerging branch of materials sciences due to their growing importance as responsive materials in diagnostics, therapeutics, and biomedical applications. The diversity provided by easily modifiable peptide sequences can be further increased by introducing nonnatural amino acids such as cyclic β-amino acids, leading to the formation of foldamers. Moreover, it is possible to combine peptide chains with other polymers, aromatic compounds, etc. to create hybrids with completely new properties and applications. In this review, we focus on the cis/trans enantiomers of three cyclic β-amino acids: 2-aminocyclobutane-1-carboxylic acid (ACBC), 2-aminocyclopentane-1-carboxylic acid (ACPC) and 2-aminocyclohexane-1-carboxylic acid (ACHC). The peptides discussed here either contain exclusively β-amino acids or are α,β-peptides, and they undergo self-assembly by forming different interactions that lead to the creation of well-defined nanostructures..