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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.


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Recent papers

Biodegradation of the aminopolyphosphonate DTPMP by the cyanobacterium Anabaena variabilis proceeds via a C–P lyase-independent pathway
Drzyzga, D.; Forlani, G.; Vermander, J.; Kafarski, P.; Lipok, J.
Environm. Microbiol. 2017, 19, 1065
DOI: 10.1111/1462-2920.13616

Abstract
Cyanobacteria, the only prokaryotes capable of oxygenic photosynthesis, play a major role in carbon, nitrogen and phosphorus global cycling. Under conditions of increased P availability and nutrient loading, some cyanobacteria are capable of blooming, rapidly multiplying and possibly altering the ecological structure of the ecosystem. Because of their ability of using non-conventional P sources,these microalgae can be used for bioremediation purposes. Under this perspective, the metabolization of the polyphosphonate diethylenetriaminepenta(methylenephosphonic) acid (DTPMP) by the strain CCALA 007 of Anabaena variabilis was investigated using 31P NMR analysis. Results showed a quantitative breakdown of DTPMP by cell-free extracts from cyanobacterial cells grown in the absence of any phosphonate. The identification of intermediates and products allowed us to propose a unique and new biodegradation pathway in which the formation of (N-acetylaminomethyphosphonic acid represents a key step. This hypothesis was strengthened by the results obtained by incubating cell-free extracts with pathway intermediates. When Anabaena cultures were grown in the presence of the phosphonate, or phosphorus-starved before the extraction, signifi cantly higher biodegradation rates were found.

Recent papers

Metabolomics analysis of fungal biofilm development and of arachidonic acid-based quorum sensing mechanism
Ząbek A, Junka A, Szymczyk P, Wojtowicz W, Klimek-Ochab M, Młynarz P
Journal of Basic Microbiology 2017, 9999, 1
DOI: 10.1002/jobm.201600636

Recent papers

Novel organophosphorus scaffolds of urease inhibitors obtained by substitution of Morita-Baylis-Hillman adducts with phosphorus nucleophiles
Ntatsopoulos, V.; Vassiliou, S.; Macegoniuk, K.; Berlicki, Ł.; Mucha, A.
Eur. J. Med. Chem. 2017, 133, 107
DOI: 10.1016/j.ejmech.2017.03.070

Abstract
The reactivity of Morita-Baylis-Hillman allyl acetates was employed to introduce phosphorus-containing functionalities to the side chain of the cinnamic acid conjugated system by nucleophilic displacement. The proximity of two acidic groups, the carboxylate and phosphonate/phosphinate groups, was necessary to form interactions in the active site of urease by recently described inhibitor frameworks. Several organophosphorus scaffolds were obtained and screened for inhibition of the bacterial urease, an enzyme that is essential for survival of urinary and gastrointestinal tract pathogens. α-Substituted phosphonomethyl- and 2-phosphonoethyl-cinnamate appeared to be the most potent and were further optimized. As a result, one of the most potent organophosphorus inhibitors of urease, α-phosphonomethyl-p-methylcinnamic acid, was identified, with Ki = 0.6 μM for Sporosarcina pasteurii urease. High complementarity to the enzyme active site was achieved with this structure, as any further modifications significantly decreased its affinity. Finally, this work describes the challenges faced in developing ligands for urease.

Recent papers

Baker’s yeasts driven synthesis of enantiomers of ethyl 1-hydroxy-1-(3,4-dimethoxyphenyl)methane(P-phenyl)phosphinate - possible organophosphorus CDA’s
Żymańczyk-Duda E, Kozyra K, Brzezińska-Rodak M, Klimek-Ochab M
Journal of Molecular Catalysis. B, Enzymatic 2017, 1
DOI: 10.1016/j.molcatb.2017.01.017

Recent papers

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products
Miszczyk, P.; Wieczorek, D.; Gałęzowska, J.; Dziuk, B.; Wietrzyk, J.; Chmielewska, E.
Molecules 2017, 22, 1
DOI: 10.3390/molecules22020254

Abstract
The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid

Recent papers

Three-Component Reaction of Benzylamines, Diethyl Phosphite and Triethyl Orthoformate: Dependence of the Reaction Course on the Structural Features of the Substrates and Reaction Conditions
Miszczyk, P.; Turowska-Tyrk, I.; Kafarski, P.; Chmielewska, E.
Molecules 2017, 22, 1
DOI: 10.3390/molecules22030450

Abstract
The reaction between benzyl amines, triethyl orthoformate, and diethyl phosphite affords either bisphosphonic or N-benzylaminobenzylphosphonic acid depending on the reaction conditions. The final output of the reaction can be manipulated by the choice of reaction conditions, particularly the molar ratio of substrates.

Recent papers

Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families
Poreba M, Szalek A, Rut W, Kasperkiewicz P, Rutkowska-Wlodarczyk I, Snipas SJ, Itoh Y, Turk D, Turk B, Overall CM, Kaczmarek L, Salvesen GS, Drag M
Scientific Reports 2017, 1
DOI: 10.1038/srep43135

Recent papers

Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling
Macegoniuk, K.; Kowalczyk, R.; Rudzińska, A.; Psurski, M.; Wietrzyk, J.; Berlicki, Ł.
Bioorg. Med. Chem. Lett. 2017, 27, 1346
DOI: 10.1016/j.bmcl.2017.02.022

Abstract
Covalent enzyme inhibitors constitute a highly important group of biologically active compounds, with numerous drugs available on the market. Although the discovery of inhibitors of urease, a urea hydrolyzing enzyme crucial for the survival of some human pathogens, is a field of medicinal chemistry that has grown in recent years, covalent urease inhibitors have been rarely investigated until now. Forty Michael acceptor-type compounds were screened for their inhibitory activities against bacterial urease, and several structures exhibited high potency in the nanomolar range. The correlation between chemical reactivity towards thiols and inhibitory potency indicated the most valuable compound — acetylenedicarboxylic acid, with View the MathML source = 42.5 nM and logkGSH = –2.14. Molecular modelling studies revealed that acetylenedicarboxylic acid is the first example of highly effective mode of binding based on simultaneous bonding to a cysteine residue and interaction with nickel ions present in the active site. Activity-reactivity profiling of reversible covalent enzyme inhibitors is a general method for the identification of valuable drug candidates.

Recent papers

Controlling the Helix Handedness of ααβ-Peptide Foldamers through Sequence Shifting
Szefczyk, M.; Węglarz-Tomczak, E.; Fortuna, P.; Krzysztoń, A.; Rudzińska-Szostak, E.; Berlicki, Ł.
Angew. Chem. Int. Ed. 2017, 56, 2087
DOI: 10.1002/anie.201610154

Abstract
Peptide foldamers containing both cis-β-aminocyclopentanecarboxylic acid and α-amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ-Peptides were found to fold into an unprecedented and well-defined 16/17/15/18/14/17-helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ-peptides, the balance between left-handed and right-handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses.

Recent papers

Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)
Drag-Zalesinska M, Drag M, Poreba M, Borska S, Kulbacka J, Saczko J
Cancer Cell International 2017, 17, 7
DOI: 10.1186/s12935-016-0369-3