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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

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

Abstract
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

Abstract
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

Abstract
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

Recent papers

Self-Assembled Protein-Aromatic Foldamer Complexes with 2:3 and 2:2:1 Stoichiometries
Jewginski, M., Granier, T., Langlois D’Estaintot, B., Fischer, L., Mackereth, C.D., Huc, I
Journal of the American Chemical Society 2017, 139, 2928
DOI: 10.1021/jacs.7b00184

Abstract
The promotion of protein dimerization using the aggregation properties of a protein ligand was explored and shown to produce complexes with unusual stoichiometries. Helical foldamer 2 was synthesized and bound to human carbonic anhydrase (HCA) using a nanomolar active site ligand. Crystal structures show that the hydrophobicity of 2 and interactions of its side chains lead to the formation of an HCA2-23 complex in which three helices of 2 are stacked, two of them being linked to an HCA molecule. The middle foldamer in the stack can be replaced by alternate sequences 3 or 5. Solution studies by CD and NMR confirm left-handedness of the helical foldamers as well as HCA dimerization.

Recent papers

A toolbox of fluorescent probes for parallel imaging reveals uneven location of serine proteases in neutrophils
Kasperkiewicz P, Altman Y, D'Angelo M, Salvesen GS, Drag M
Journal of the American Chemical Society 2017, 139, 10115
DOI: 10.1021/jacs.7b04394

Recent papers

Addition of thiols to the double bond of dipeptide C -terminal dehydroalanine as a source of new inhibitors of cathepsin C
Lenartowicz, P.; Makowski, M.; Oszywa, B.; Haremza, K.; Latajka, R.; Pawełczak, M.; Kafarski, P.
Biochimie 2017, 139, 46
DOI: 10.1016/j.biochi.2017.05.011

Abstract
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors. This was proved by TLC analysis of the medium in which interaction of methyl (S)-phenylalanyl-(R,S)-(S-adamantyl)cysteinate (7i) with the enzyme was studied. Molecular modeling enabled to establish their mode of binding showed that S2 pocket is long and narrow and accommodates phenyl group of phenylalanine while significantly spacious sites located at the surface of the enzyme (one of them being S1 pocket) bind the adamantyl moiety oriented in different direction for each stereoisomer. Finally replacement of carboxymethyl moiety of methyl (S)-phenylalanyl-(R,S)-(S-phenyl)cysteinate (7c) with nitrile group provided about 650-times more potent inhibitor of cathepsin C indicating that the studied C-terminal S-substituted cysteines are good activity probes for S1 binding pocket of this enzyme.

Recent papers

Diethyl boronobenzylphosphonates as substrates in Suzuki–Miyaura reaction
Rydzewska, A.; Mangold, A,; Wanat, W.; Kafarski, P.
Phosphorus, Sulfur, Silicon Relat. Elements 2017, 192, 758
DOI: 10.1080/10426507.2017.1284845

Abstract
N-substituted boronobenzylphosphonates were evaluated as substrates in Suzuki–Miyaura couplingcatalyzed by tetrakis(triphenylphosphine)palladium(0) and complex of palladium acetate and (2-biphenyl)dicyclohexylphosphine. It was proven that they may be considered as useful substrates for thepreparation of functionalized aminophosphonates.

Recent papers

Michael additions to double bonds of esters of N-protected (s)-phenylalanyldehydroalanine (X-(s)-Phe-ΔAla-OMe) and its phosphonic acid counterpart (X-(s)-Phe-ΔAla-PO(OEt)2)
Lenartowicz, P., Dziuk, B.; Zarychta, B.; Makowski, M.; Kafarski P.
Phosphorus, Sulfur, Silicon Relat. Elements 2017, 192, 706
DOI: 10.1080/10426507.2017.1308933

Abstract
Electrophilic addition of amines, thiols and bromide to the double bonds of model dehydrodipeptides and dehydrophosphonodipeptide was studied. The double bond in these two classes of peptides reacted similarly and gave the same products. These results indicate that dehydropeptides are very good candidates assubstrates for modifications of peptide side-chain

Recent papers

Synthesis of fluorescent aminophosphonates by green chemistry proced
Kuśnierz, A.; Chmielewska E,
Phosphorus, Sulfur, Silicon Relat. Elements 2017, 192, 700
DOI: 10.1080/10426507.2017.130

Abstract
Fluorescent aminophosphonates were obtained using optimized conditions of the microwave-stimulatedKabachnik-Fields reaction. Unfortunately, in the case of more demanding, bulky amines and aldehydes thisreaction failed to give the desired products.