Department of Bioorganic Chemistry is one of 14 departments of Faculty of Chemistry, Wrocław University of Science and Technology. It is headed by Łukasz Berlicki and formed by 5 research groups of: prof. Paweł Kafarski, prof. Artur Mucha, prof. Łukasz Berlicki, prof. Rafał Latajka and Dr. Rafał Kowalczyk. The main research areas are on a border of chemistry and biology.
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[EN] We would like to kindly invite you to the lecture of Prof. Paula Gomes from the University of Porto entitled “From...Opublikowany przez Berlicki Lab Czwartek, 6 października 2022
Recent papers Tailoring peptides and peptidomimetics for targeting protein-protein interactions
Berlicki, Ł. in Peptide and Peptidomimetic Therapeutics (N. Qvit, S. J. S. Rubin Eds.) 2022
, 57DOI: 10.1016/B978-0-12-820141-1.00009-1 Abstract
Protein-protein interactions (PPI) are involved in the control of numerous processes in living cells and are also related to pathogenic states. Therefore, they are considered valuable drug targets. Peptides and peptidomimetics are classes of compounds that are excellent for construction of PPI inhibitors due to their relatively large size, synthetic availability, and controllable three-dimensional structure. This chapter reviews various approaches for construction of peptide-based PPI inhibitors divided according to their secondary structures (helices, extended structures, and loops).
Recent papers Role of Helical Structure in MBP Immunodominant Peptides for Efficient IgM Antibody Recognition in Multiple Sclerosis
A. Staśkiewicz, M. Quagliata, F. Real-Fernandez, F. Nuti, R. Lanzillo, V. Brescia-Morra, H. Rusche, M. Jewginski, A. Carotenuto, D. Brancaccio, R. Aharoni, R. Arnon, P. Rovero, R. Latajka, A. M. Papini Frontiers in Chemistry 2022
, 885180DOI: doi.org/10.3389/fchem.2022.885180Abstract
The involvement of Myelin Basic Protein (MBP) in Multiple Sclerosis (MS) has been widely discussed in the literature. This intrinsically disordered protein has an interesting α-helix motif, which can be considered as a conformational epitope. In this work we investigate the importance of the helical structure in antibody recognition by MBP peptides of different lengths. Firstly, we synthesized the peptide MBP (81–106) (1) and observed that its elongation at both N- and C-termini, to obtain the peptide MBP (76–116) (2) improves IgM
antibody recognition in SP-ELISA, but destabilizes the helical structure. Conversely, in competitive ELISA, MBP (81–106) (1) is recognized more efficiently by IgM antibodies than MBP (76–116) (2), possibly thanks to its more stable helical structure observed in CD and NMR conformational experiments. These results are discussed in terms of different performances of peptide antigens in the two ELISA formats tested.
Recent papers Synthesis of Hybrid Tripeptide Peptidomimetics Containing Dehydroamino Acid and Aminophosphonic Acid in the Chain and Evaluation of Their Activity toward Cathepsin C
Jewgiński, M; Makowski, M.; Pawełczak, M.; Goldeman, W.; Trojanowska-Laskowska, A.; Kafarski, P.; Latajka, R. Chemistry and Biodiversity 2022
, accepted.DOI: 10.1002/cbdv.202101019 Abstract
Synthesis of a new group of hybrid phosphonodehydropeptides composed of glycyl-(Z)-dehydrophenylalanine and structurally variable aminophosphonates alongside with investigations of their activity towards cathepsin C are presented. Obtained results suggest that the introduction of (Z)-dehydrophenylalanine residue into the short phosphonopeptide chain does induce the ordered conformation. Investigated peptides appeared to act as weak or moderate inhibitors of cathepsin C. © 2022 Wiley-VHCA AG, Zurich, Switzerland.
Recent papers Miniproteins in medicinal chemistry
Ciesiołkiewicz, A.; Lizandra Perez, J.; Berlicki, Ł. Bioorg. Med. Chem. Lett. 2022
, 128806DOI: 10.1016/j.bmcl.2022.128806 Abstract
Miniproteins exhibit great potential as scaffolds for drug candidates due to their well-defined structure and good synthetic availability. Because of recently described methodologies for their de novo design, the field of miniproteins is emerging and can provide molecules that effectively bind to problematic targets, i.e., those that have been previously considered to be undruggable. This review describes methodologies for the development of miniprotein scaffolds as well as for the construction of biologically active miniproteins.
Recent papers Design and Engineering of Miniproteins
Ożga, K.; Berlicki, Ł. ACS Bio Med Chem Au 2022
, 316DOI: 10.1021/acsbiomedchemau.2c00008 Abstract
The potential of miniproteins in the biological and chemical sciences is constantly increasing. Significant progress in the design methodologies has been achieved over the last 30 years. Early approaches based on propensities of individual amino acid residues to form individual secondary structures were subsequently improved by structural analyses using NMR spectroscopy and crystallography. Consequently, computational algorithms were developed, which are now highly successful in designing structures with accuracy often close to atomic range. Further perspectives include construction of miniproteins incorporating non-native secondary structures derived from sequences with units other than α-amino acids. Noteworthy, miniproteins with extended structures, which are now feasibly accessible, are excellent scaffolds for construction of functional molecules.
Recent papers Rational Development of Bacterial Ureases Inhibitors
Loharch, S.; Berlicki, Ł. Chem. Rec. 2022
, accepted.DOI: 10.1002/tcr.202200026 Abstract
Urease, an enzyme that catalyzes the hydrolysis of urea, is a virulence factor of various pathogenic bacteria. In particular, Helicobacter pylori, that colonizes the digestive tract and Proteus spp., that can infect the urinary tract, are related to urease activity. Therefore, urease inhibitors are considered as potential therapeutics against these infections. This review describes current knowledge of the structures, activity, and biological importance of bacterial ureases. Moreover, the structure-based design of several classes of bacterial urease inhibitors is presented and discussed. Phosphinic and phosphonic acids were applied as transition-state analogues, while Michael acceptors and ebselen derivatives were applied as covalent binders of cysteine residue. This review incorporates bacterial urease inhibitors from literature published between 2008 and 2021.
Recent papers Synthesis of Tetrapeptides Containing Dehydroalanine, Dehydrophenylalanine and Oxazole as Building Blocks for Construction of Foldamers and Bioinspired Catalysts
Lenartowicz, P.; Beelen, M.; Makowski, M.; Wanat, W.; Dziuk, B. Kafarski, P. Molecules 2022
, 1DOI: 10.3390/molecules27092611 Abstract
The incorporation of dehydroamino acid or fragments of oxazole into peptide chain is accompanied by a distorted three-dimensional structure and additionally enables the introduction of non-typical side-chain substituents. Thus, such compounds could be building blocks for obtaining novel foldamers and/or artificial enzymes (artzymes). In this paper, effective synthetic procedures leading to such building blocks—tetrapeptides containing glycyldehydroalanine, glycyldehydrophenylalanine, and glycyloxazole subunits—are described. Peptides containing serine were used as substrates for their conversion into peptides containing dehydroalanine and aminomethyloxazole- 4-carboxylic acid while considering possible requirements for the introduction of these fragments into long-chain peptides at the last steps of synthesis.
Recent papers Challenges in Experimental Methods. In: Computer Simulations of Aggregation of Proteins and Peptides. Methods in Molecular Biology
Gąsior-Głogowska M. E., Szulc N., Szefczyk M. Humana, New York 2022
, 281DOI: 10.1007/978-1-0716-1546-1_13Abstract
Experimental studies of amyloids encounter many challenges. There are many methods available for studying proteins, which can be applied to amyloids: from basic staining techniques, allowing visualization of fibers, to complex methods, e.g., AFM-IR used to their detailed biochemical and structural characterization in nanoscale. Which method is appropriate depends on the goal of an experiment: verification of aggregational properties of a peptide, distinguishing oligomers from mature fibers, or kinetic studies. Insolubility, rapid aggregation, and the need of using a high-purity peptide may be a limiting factor in studies involving amyloids. Moreover, the results obtained by various experimental methods often differ significantly, which may lead to misclassification of amyloid peptides. Due to ambiguity of experimental results, laborious and time-consuming analysis, bioinformatical methods become more widely used for amyloids.
Recent papers Controlling the conformational stability of coiled-coil peptides with a single stereogenic center of a peripheral β-amino acid residue
Szefczyk, M.; Ożga, K.; Drewniak-Świtalska, M.; Rudzińska-Szostak, E.; Hołubowicz, R.; Ożyhar, A.; Berlicki, Ł. RSC Adv. 2022
, 4640DOI: 10.1039/D2RA00111J 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.
Recent papers Peptide stapling by late-stage Suzuki–Miyaura cross-coupling
Hendrik Gruß, Rebecca C. Feiner, Ridhiwan Mseya, David C. Schröder, Michał Jewgiński, Kristian M. Müller, Rafał Latajka, Antoine Marion, Norbert Sewald Beilstein Journal of Organic Chemistry 2022
, 1DOI: https://doi.org/10.3762/bjoc.18.1 Abstract
The development of peptide stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein–protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki–Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated