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Department of Bioorganic Chemistry is one of 15 departments of Faculty of Chemistry, Wrocław University of Technology. It was founded in 1971 by Professor Przemysław Mastalerz in response to introduction of biochemistry and biotechnology curricula at Faculty of Chemistry. Now it is headed by Professor Paweł Kafarski and formed by 6 professors, 10 assistant professors and over 25 PhD students doing research on a border of chemistry and biology.





Recent papers

Yeast as a Versatile Tool in Biotechnology
Zymańczyk-Duda E, Brzezińska-Rodak M, Klimek-Ochab M, Duda M, Zerka A
Yeast - Industrial Applications, Prof A.Morata (Ed) InTech 2017, 1
DOI: 10.5772/intechopen.70130

Recent papers

Nanokrzemionka - bioperspektywa i potencjał przemysłowy. Cz. 1.
Fajfer D., Zielonka A., Klimek-Ochab M.
Laboratorium-Przegląd Ogólnopolski 2017, 49
Nanotechnologia jest bardzo szybko rozwijającą się dziedziną nauki. W ostatnich latach szczególną uwagę poświęcono cząstkom o wymiarach nano, które posiadają szeroki zakres zastosowań w przemyśle spożywczym, papierniczym, ceramicznym, budowlanym, medycznym oraz rolnym. Jedną z takich nanocząstek jest nanokrzemionka, której synteza biometodami zyskuje coraz większe zainteresowanie ze względu na ich ekonomiczność oraz neutralność wobec środowiska. W niniejszej publikacji przedstawiono formę występowania nanokrzemionki wykorzystywaną podczas biokonwersji roślin, które są bogate w ten cenny składnik. Zaprezentowano również mechanizm jej biopozyskiwania w porównaniu z metodami chemicznymi i fizycznymi, a także jej szeroki zakres aplikacyjny.

Recent papers

Fungal synthesis of size-defined nanoparticles
Zielonka A., Klimek-Ochab M.
Advances in Natural Sciences-Nanoscience and Nanotechnology 2017, 8, 1
Fungi with metabolic capacities can efficiently synthesize a wide range of nanoparticles (NPs).

This biotransformation process and its product have extensive applications especially for industry, agriculture and medicine, where NPs size and shape is essential and can be defined by specific analytical methods. Fungi cultivation and further bioconversion can be fully controlled to obtain the desired nanoparticles. Additionally, this review provides information about the

fungus F. oxysporum, which is able to synthesize the largest amount of different types of NPs.

Recent papers

New aspects of coordination chemistry and biological activity of NTMP-related diphosphonates containing a heterocyclic ring
Gałęzowska, J.; Czapor-Irzabek, H.; Janicki, R.; Chmielewska, E.; Janek, T.
New J. Chem. 2017, 41, 10731
DOI: 10.1039/c7nj02415k

Two analogues of nitrilotris(methylene-phosphonic acid) (NTMP), namely L1 = N-(methylene-2-pyridine)-N,N,-di-(methylenephosphonate) and L2 = N-(methylene-1H-benzimidazol)-N,N,-di-(methylenephosphonate)in which one of the phosphonic arms was replaced by a heterocyclic moiety, pyridine and benzimidazole, were studied in terms of coordination chemistry towards transition (Cu2+, Ni2+, Zn2+) and alkaline-earth metal ions (Ca2+ and Mg2+) by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC). The cytotoxicity of the ligands as well as their Zn2+, Ca2+ and Mg2+ complexes was tested against various cell lines (human melanoma A375 and human colon adenocarcinoma HT29) revealing a selective antitumor effect in vivo. Both of the ligands exhibit a potent inhibitory effect on tumor cell migration and experimental metastasis. Potentiometric and ESI-MS measurements have shown the existence of monomeric species only, without the presence of biscomplexes or polynuclear species. The conditional stability constants (log Kc) of the Zn2+, Ca2+, and Mg2+ complexes were determined independently by two methods for both of the studied ligands and are a first example of comprehensive potentiometry/ITC studies made for phosphonic acid complexation. No significant differentiation in coordination models for the studied set of metal ions was noticed; however, as expected due to the different metal ion natures, the complexes revealed dissimilar thermodynamic stability and behavior, depending on the metal ion and pH used. The possible structures of the complexes formed are discussed on the basis of spectroscopic and spectrometric results.

Recent papers

Bioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint
Magiera-Mularz, K.; Skalniak, L.; Zak, K. M.; Musielak, B.; Rudzinska-Szostak, E.; Berlicki, Ł.; Kocik, J.; Grudnik, P.; Sala, D. Zarganes-Tzitzikas, T.; Shaabani, S.; Dömling, A.; Dubin, G.; Holak, T. A.
Angew. Chem. Int. Ed. 2017, 56, 13732
DOI: 10.1002/anie.201707707

Blockade of the immunoinhibitory PD-1/PD-L1 pathway using monoclonal antibodies has shown impressive results with durable clinical antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have now been approved for the treatment of a number of tumor types, whereas the development of small molecules targeting immune checkpoints lags far behind. We characterized two classes of macrocyclic-peptide inhibitors directed at the PD-1/PD-L1 pathway. We show that these macrocyclic compounds act by directly binding to PD-L1 and that they are capable of antagonizing PD-L1 signaling and, similarly to antibodies, can restore the function of T-cells. We also provide the crystal structures of two of these small-molecule inhibitors bound to PD-L1. The structures provide a rationale for the checkpoint inhibition by these small molecules, and a description of their small molecule/PD-L1 interfaces provides a blueprint for the design of small-molecule inhibitors of the PD-1/PD-L1 pathway.

Recent papers

Synthesis of a HyCoSuL peptide substrate library to dissect protease substrate specificity
Poreba M, Salvesen GS, Drag M
Nature Protocols 2017, 12, 2189
DOI: 10.1038/nprot.2017.091

Recent papers

Sequence engineering to control the helix handedness of peptide foldamers
Rudzińska-Szostak, E.; Berlicki, Ł.
Chem. Eur. J. 2017, 23, 14980
DOI: 10.1002/chem.201702730

Peptide foldamers have been studied for over two decades and numerous sequence patterns have been shown to form well-defined three-dimensional arrangements in solution. In particular, helices of various geometries have been described. In this article, different concepts concerning the construction of helical foldameric peptides, for which the possibility of governing the sense of the formed helix was evidenced, are presented and discussed.

Recent papers

Aminophosphinates against Helicobacter pylori ureolysis—Biochemical and whole-cell inhibition characteristics
Macegoniuk, K.; Grela, E.; Biernat, M.; Psurski, M.; Gościniak, G.; Dziełak, A.; Mucha, A.; Wietrzyk, J.; Berlicki, Ł.; Grabowiecka, A.
PLoS One 2017, 1, 182437
DOI: 10.1371/journal.pone.0182437

Urease is an important virulence factor from Helicobacter pylori that enables bacterial colonization of human gastric mucosa. Specific inhibition of urease activity can be regarded as a promising adjuvant strategy for eradication of this pathogen. A group of organophosphorus inhibitors of urease, namely, aminophosphinic acid and aminophosphonic acid derivatives, were evaluated in vitro against H. pylori urease. The kinetic characteristics of recombinant enzyme activity demonstrated a competitive reversible mode of inhibition with Ki values ranging from 0.294 to 878 μM. N-n-Hexylaminomethyl-P-aminomethylphosphinic acid and N-methylaminomethyl-P-hydroxymethylphosphinic acid were the most effective inhibitors (Ki = 0.294 μM and 1.032 μM, respectively, compared to Ki = 23 μM for the established urease inhibitor acetohydroxamic acid). The biological relevance of the inhibitors was verified in vitro against a ureolytically active Escherichia coli Rosetta host that expressed H. pylori urease and against a reference strain, H. pylori J99 (CagA+/VacA+). The majority of the studied compounds exhibited urease-inhibiting activity in these whole-cell systems. Bis(N-methylaminomethyl)phosphinic acid was found to be the most effective inhibitor in the susceptibility profile studies of H. pylori J99. The cytotoxicity of nine structurally varied inhibitors was evaluated against four normal human cell lines and was found to be negligible.

Recent papers

Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity
Wavhale, R. D.; Martis, E. A. F.; Ambre, P. K.; Wan, B.; Franzblau, S. G.; Iyer, K. R.; Raikuvar, K.; Macegoniuk, K.; Berlicki, Ł.; Nandan, S. R.; Coutinho, E. C.
Bioorg. Med. Chem. 2017, 25, 4835
DOI: 10.1016/j.bmc.2017.07.034

BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles – 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, 1H NMR, 13C NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 μg/ml vs 0.7–1.5 μg/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 µM vs 7.8 µM).

Recent papers

Biodiversity in targeted metabolomics analysis of filamentous fungal pathogens by 1H NMR-based studies
Ząbek A, Klimek-Ochab M, Jawień E, Młynarz P
World J Microbiol Biotechnol 2017, 33, 132
DOI: DOI 10.1007/s11274-017-2285-7