Main Page

From Bioorganic
Revision as of 07:47, 5 November 2020 by Berlicki (Talk | contribs)

Jump to: navigation, search

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, Dr. Rafał Kowalczyk and Dr. Rafał Latajka. The main research areas are on a border of chemistry and biology.





Find Department of Bioorganic Chemistry and Berlicki Lab on Facebook and Twitter.

[EN] MSc. Agnieszka Ciesiołkiewicz, a PhD student at Berlicki Lab, received the Rector's distinction for her activity...

Opublikowany przez Berlicki Lab Poniedziałek, 2 listopada 2020

Recent papers

Hypervalent-iodine mediated one-pot synthesis of isoxazolines and isoxazoles bearing a difluoromethyl phosphonate moiety
Pajkert, R.; Koroniak, H.; Kafarski, P.; Röschenthaler, G.-V.
Org. Biomol. Chem. 2021, 19, 4871
DOI: 10.1039/d1ob00685a

A one-pot, regioselective 1,3-dipolar cycloaddition of in situ generated (diethoxyphosphoryl)difluoromethyl nitrile oxide toward selected alkenes and alkynes is reported. This protocol enables facile access to 3,5-disubstituted isoxazolines and isoxazoles bearing a CF2P(O)(OEt)2 moiety in good to excellent yields, under mild reaction conditions.

Recent papers

Peptides and Peptidomimetics as Inhibitors of Enzymes Involved in Fibrillar Collagen Degradation
Ledwoń P., Papini A.M., Rovero P., Latajka R.
Materials 2021, 14, 3217

Recent papers

Searching for universal model of amyloid signaling motifs using probabilistic context-free grammars
Dyrka, W.; Gąsior-Głogowska, M.; Szefczyk, M.; Szulc, N.
BMC Bioinformatics 2021, 22, 222
DOI: 10.1186/s12859-021-04139-y
Amyloid signaling motifs are a class of protein motifs which share basic structural and functional features despite the lack of clear sequence homology. They are hard to detect in large sequence databases either with the alignment-based profile methods (due to short length and diversity) or with generic amyloid- and prion-finding tools (due to insufficient discriminative power). We propose to address the challenge with a machine learning grammatical model capable of generalizing over diverse collections of unaligned yet related motifs. First, we introduce and test improvements to our probabilistic context-free grammar framework for protein sequences that allow for inferring more sophisticated models achieving high sensitivity at low false positive rates. Then, we infer universal grammars for a collection of recently identified bacterial amyloid signaling motifs and demonstrate that the method is capable of generalizing by successfully searching for related motifs in fungi. The results are compared to available alternative methods. Finally, we conduct spectroscopy and staining analyses of selected peptides to verify their structural and functional relationship. While the profile HMMs remain the method of choice for modeling homologous sets of sequences, PCFGs seem more suitable for building meta-family descriptors and extrapolating beyond the seed sample.

Recent papers

Variability of amyloid propensity in imperfect repeats of CsgA protein of Salmonella enterica and Escherichia coli
Szulc, N.; Gąsior-Głogowska, M.; Wojciechowski, J. W.; Szefczyk, M.; Żak, A.; Burdukiewicz, M.; Kotulska, M.
Int. J. Mol. Sci. 2021, 22, 5127
DOI: 10.3390/ijms22105127

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.

Recent papers

Triazole-modified peptidomimetics: an opportunity for drug discovery and development
A. Staśkiewicz, P. Ledwoń, P. Rovero, A.M. Papini, R. Latajka
Frontiers in Chemistry 2021, 9, 674705
Peptidomimetics play a fundamental role in drug design due to their preferential properties regarding natural peptides. In particular, compounds possessing nitrogen-containing heterocycles have been intensively studied in recent years. The triazolyl moiety incorporation decreases the molecule susceptibility to enzymatic degradation, reduction, hydrolysis, and oxidation. In fact, peptides containing triazole rings are a typical example of peptidomimetics. They have all the advantages over classic peptides. Both efficient synthetic methods and biological activity make these systems an interesting and promising object of research. Peptide triazole derivatives display a diversity of biological properties and can be obtained via numerous synthetic strategies. In this review, we have highlighted the importance of the triazole-modified peptidomimetics in the field of drug design. We present an overview on new achievements in triazolyl-containing peptidomimetics synthesis and their biological activity as inhibitors of enzymes or against cancer, viruses, bacteria, or fungi. The relevance of above-mentioned compounds was confirmed by their comparison with unmodified peptides.

Recent papers

Autofluorescence of Amyloids Determined by Enantiomeric Composition of Peptides
Grelich-Mucha, M.; Garcia, A. M.; Torbeev, V.; Ożga, K.; Berlicki, Ł.; Olesiak-Bańska, J.
J. Phys. Chem. B 2021, 125, 5502
DOI: 10.1021/acs.jpcb.1c00808

Amyloid fibrils are peptide or protein aggregates possessing a cross-β-sheet structure. They possess intrinsic fluorescence property, which is still not fully understood. Herein, we compare structural and optical properties of fibrils formed from L- and D-enantiomers of the (105–115) fragment of transthyretin (TTR) and from their racemic mixture. Our results show that autofluorescence of fibrils obtained from enantiomers differs from that of fibrils from the racemic mixture. In order to elucidate the origin of observed differences, we analyzed the structure and morphology of fibrils and showed how variations in β-sheet organization influence optical properties of fibrils. We clarified the contribution of aromatic rings and the amyloid backbone to the final blue-green emission of fibrils. This work demonstrates how enantiomeric composition of amino acids allows us to modulate the self-assembly and final morphology of well-defined fibrillar bionanostructures with optical properties controlled by supramolecular organization.

Recent papers

Phosphinotripeptidic Inhibitors of Leucylaminopeptidases
Jewgiński M., Haremza K, de los Santos J.M, Es Sbai Z, Oszywa B, Pawełczak M, Palacios F, Latajka R
International Journal of Molecular Science 2021, 22, 590
DOI: 10.3390/ijms22105090

Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate oseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor

activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate L-Leu-p-nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Sus scrofa Leucine aminopeptidase) and barley seeds (HvLAP, Hordeum vulgare Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test

shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.

Recent papers

A computationally designed β-amino acid-containing miniprotein.
Bejger, M.; Fortuna, P.; Drewniak, M.; Plewka, J.; Rypniewski, W.; Berlicki, Ł.
Chem. Commun. 2021, 57, 6015
DOI: 10.1039/D1CC02192C

A new miniprotein built from three helices, including one structure based on a ααβαααβ sequence pattern was developed. Its crystal structure revealed a compact conformation with a well-packed hydrophobic core of unprecedented structure. The miniprotein formed dimers that were stabilized by an interaction of the hydrophobic surfaces.

Recent papers

Towards Foldameric Miniproteins: A Helix‐Turn‐Helix Motif
Ożga, K.; Drewniak-Świtalska, M.; Rudzińska-Szostak, E.; Berlicki, Ł.
ChemPlusChem 2021, 86, 646
DOI: 10.1002/cplu.202100090

Numerous beta‐amino acid containing peptides forming secondary structures have been already described, however the design of higher order structures remains poorly explored. The methodology allowing construction of sequence patterns containing few rigid secondary element was proposed and experimentally validated. On a basis of 9/10/9/12‐helix containing cis‐2‐aminocyclopentanecarboxylic acid (cis‐ACPC) residues arranged in aabb sequence pattern, a conformationally stable helix‐turn‐helix structure was designed. The connection between two helices was also constructed using cis‐ACPC residues. Five examples of designed peptides were obtained and analyzed using circular dichroism and nuclear magnetic resonance spectroscopies, which confirmed the assumed way of folding. The NMR structure was calculated for the peptide with the highest number of non‐sequential contacts.

Recent papers

Constrained beta-amino acid-containing miniproteins
Drewniak, M.; Barycza, B.; Rudzińska-Szostak, E.; Morawiak, P.; Berlicki, Ł.
Org. Biomol. Chem. 2021, 19, 4272
DOI: 10.1039/D1OB00309G

The construction of beta-amino acid-containing peptides that fold to tertiary structures in solution remains challenging. Two model miniproteins, namely, Trp-cage and FSD, were scanned using constrained beta-amino acid in order to evaluate its impact on the folding process. Relationships between forces stabilizing miniprotein structure and conformational stability of analogues were found. The possibility of significant increase of a conformational stability of studied miniproteins by substitution with beta-amino acid at terminus of a helix was shown. On the basis of these results, beta-amino acid containing-peptide analogs with helical fragments substantially altered by incorporation of several constrained beta-amino acids were designed, synthesized and evaluated with respect to their structure and stability. The smallest known -amino acid-containing peptide with well-defined tertiary structure is described.