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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.


Members

Research

Publications


News

Open positions for PhD student and Postdoc to work at project "Foldameric miniproteins - structure and catalytic function".

Konkurs na stypendium dla doktoranta oraz na stanowisko asystenta naukowego do pracy przy projekcie "Minibiałka forldamerowe - struktura i funkcja katalityczna".


Recent papers

Substituted phosphonic analogues of phenylglycine as inhibitors of phenylalanine ammonia lyase from potatoes
Weronika Wanat, Michał Talma, Józef Hurek, Małgorzata Pawełczak, Paweł Kafarski
Biochimie 2018, 151, 119
DOI: https://doi.org/10.1016/j.biochi.2018.06.005
Abstract
A series of phosphonic acid analogues of phenylglycine variously substituted in phenyl ring have been synthesized and evaluated for their inhibitory activity towards potato l-phenylalanine ammonia lyase. Most of the compounds appeared to act as moderate (micromolar) inhibitors of the enzyme. Analysis of their binding performed using molecular modeling have shown that they might be bound either in active site of the enzyme or in the non-physiologic site. The latter one is located in adjoining deep site nearby the to the entrance channel for substrate into active site.

Recent papers

Recent advances in design of new urease inhibitors: A review
P. Kafarski, M. Talma
Journal of Advanced Research 2018, 1, 1
DOI: https://doi.org/10.1016/j.jare.2018.01.007
Abstract
Urease is a nickel-dependent metalloenzyme found in plants, some bacteria, and fungi. Bacterial enzyme\r\nis of special importance since it has been demonstrated as a potent virulence factor for some species.\r\nEspecially it is central to Helicobacter pylori metabolism and virulence being necessary for its colonization\r\nof the gastric mucosa, and is a potent immunogen that elicits a vigorous immune response. Therefore, it is\r\nnot surprising that efforts to design, synthesize and evaluate of new inhibitors of urease are and active\r\nfield of medicinal chemistry. In this paper recent advances on this field are reviewed.

Recent papers

Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs
Ewelina Węglarz-Tomczak, Michał Talma, Mirosław Giurg, Hans V. Westerhoff, Robert Janowski and Artur Mucha
Oncotarget 2018, 9, 29365
DOI: https://doi.org/10.18632/oncotarget.25532
Abstract
The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X2 are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (Ki in the micromolar range). The mode of action for all four compounds and both enzymes was demonstrated by molecular modeling and docking in the corresponding active sites. This knowledge gives new perspectives to Actinomycin D’s action on tumors and suggests new avenues and molecules for medical applications.

Recent papers

Selective substrates and activity-based probes for imaging of the human constitutive 20S proteasome in cells and blood samples
Rut W, Poreba M, Kasperkiewicz P, Snipas SJ, Drag M
Journal of Medicinal Chemistry 2018, 1
DOI: 10.1021/acs.jmedchem.8b00026

Recent papers

Aminobisphosphonates based on cyclohexane backbone as coordinating agents for metal ions. Thermodynamic, spectroscopic and biological studies
Gałęzowska, J.; Czapor-Irzabek, H.; Chmielewska, E.; Kafarski, P.; Janek, T.
New J. Chem. 2018, 42, 7723
DOI: 10.1039/c8nj01158c

Abstract
Single and double amino-bisphosphonates were synthesized and tested for coordination capabilities towards Ca2+, Mg2+, Cu2+ and Ni2+ metal ions by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC), as well as for cytotoxic activity by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Half minimal inhibitory concentrations (IC50) were determined with respect to two cell lines (human melanoma A375 and human colorectal adenocarcinoma HT29). Basing the structure of compounds on a cyclohexane ring allowed for a slight reduction of high hydrophilic character of the studied bisphosphonates (BPs). The ligands efficiently bind the examined metal ions forming complex equilibria with diversified stoichiometry of equimolar, polynuclear species and biscomplexes. Both ligands as well as their Ca2+ and Mg2+ complexes show selective antiproliferative activity toward the studied cancer cell lines. Given the thermodynamic and biological data, it can be assumed that ligands are good candidates for linking compounds that may be used in the design of new drug delivery systems. In this approach, one bisphosphonate moiety acts as a bone-targeting molecule, while another molecule can be readily attached to the second donor function (primary amine or bisphosphonate).

Recent papers

Aminobisphosphonates based on cyclohexane backbone as coordinating agents for metal ions. Thermodynamic, spectroscopic and biological studies
Gałęzowska, J.; Czapor-Irabek, H.; Chmielewska, E; Kafarski, P.; Janek, T.
New J. Chem. 2018, 42, 7723
DOI: 10.1039/c8nj01158c

Abstract
Single and double amino-bisphosphonates were synthesized and tested for coordination capabilities towards Ca2+, Mg2+, Cu2+ and Ni2+ metal ions by means of potentiometry, UV-vis spectroscopy, mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC), as well as for cytotoxic activity by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Half minimal inhibitory concentrations (IC50) were determined with respect to two cell lines (human melanoma A375 and human colorectal adenocarcinoma HT29). Basing the structure of compounds on a cyclohexane ring allowed for a slight reduction of high hydrophilic character of the studied bisphosphonates (BPs). The ligands efficiently bind the examined metal ions forming complex equilibria with diversified stoichiometry of equimolar, polynuclear species and biscomplexes. Both ligands as well as their Ca2+ and Mg2+ complexes show selective antiproliferative activity toward the studied cancer cell lines. Given the thermodynamic and biological data, it can be assumed that ligands are good candidates for linking compounds that may be used in the design of new drug delivery systems. In this approach, one bisphosphonate moiety acts as a bone-targeting molecule, while another molecule can be readily attached to the second donor function (primary amine or bisphosphonate).

Recent papers

Non-symmetrical bis(aminoalkyl)phosphinates: new ligands with enhanced binding of Cu(II) ions.
Piasta, K.; Dziełak, A.; Mucha, A.; Gumienna-Kontecka, E.
New J. Chem. 2018, 42, 7737
DOI: DOI: 10.1039/c8nj01094c
Abstract
Three novel, non-symmetrical bis(aminoalkyl)phosphinic acids, L1–L3, have been synthesized and characterized. Solution studies on the coordination abilities of the ligands have shown that these compounds form various protonated mono- and bis-complexes, where copper(II) coordination is realized through the nitrogen atom(s) of the amino group(s), supported by oxygen(s) from the phosphinate unit(s). Potentiometric titrations and a full spectroscopic analysis clarified the species distribution profiles and detailed coordination modes. The results show that L1–L3 ligands are efficient chelating agents for Cu(II) ions; their metal binding abilities were compared to structurally related compounds described earlier in the literature.

Recent papers

Screening Combinatorial Peptide Libraries in Protease Inhibitor Drug Discovery
Poreba M, Kasperkiewicz P, Rut W, Drag M
Extracellular Targeting of Cell Signaling in Cancer: Strategies Directed at MET and RON Receptor Tyrosine Kinase Pathways, 1 2018, 1
DOI: 10.1002/9781119300229.ch11

Recent papers

Caspase selective reagents for diagnosing apoptotic mechanisms
Poreba M, Groborz K, Navarro M, Snipas SJ, Drag M, Salvesen GS
Cell Death and Differentiation 2018, 1
DOI: 10.1038/s41418-018-0110-y

Recent papers

Nanosilica synthesis mediated by Aspergillus parasiticus strain.
Pieła A, Żymańczyk-Duda E, Brzezińska-Rodak M, Duda M, Grzesiak J, Klimek-Ochab M
Fungal Biology 2018, 1
DOI: 10.1016/j.funbio.2018.02.004